Page last updated: 2024-11-07

tafenoquine

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Description

Tafenoquine is an antimalarial drug that was originally developed in the 1980s. It is a derivative of the antimalarial drug chloroquine and is effective against both Plasmodium falciparum and Plasmodium vivax malaria. Tafenoquine has a long half-life, which allows for single-dose treatment of malaria. Research on tafenoquine is ongoing. It is studied for its potential to reduce the risk of malaria recurrence in individuals who have been infected with P. vivax. The drug is also being investigated for its potential to prevent malaria in individuals who are at risk of infection. Tafenoquine has been approved by the US Food and Drug Administration (FDA) for the treatment of malaria and the prevention of malaria recurrence in individuals with P. vivax malaria.'

tafenoquine : A racemate comprising equimolar amounts of (R)- and (S)-tafenoquine. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

N(4)-{2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl}pentane-1,4-diamine : An aminoquinoline that is 8-aminoquinoline which is substituted by methoxy groups at positions 2 and 6, a methyl group at position 4, and a m-(trifluoromethyl)phenoxy group at position 5, and in which the amino substituent at position 8 is itself substituted by a 5-aminopentan-2-yl group. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID115358
CHEMBL ID298470
CHEBI ID141487
CHEBI ID135752
SCHEMBL ID347388
MeSH IDM0355080

Synonyms (54)

Synonym
n4-[2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolyl]pentane-1,4-diamine
wr 238605
wr238605
106635-80-7
tafenoquine
(4-amino-1-methylbutyl){2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy](8-quinolyl)}amine
1,4-pentanediamine, n4-[2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinyl]-
sb-252263
etaquine
(rs)-n(sup 3)-(2,6-dimethoxy-4-methyl-5-(3-trifluoro-methylphenoxy)quinolin-8-yl)pentane-1,4-diamine
(r)-n3-(2,6-dimethoxy-4-methyl-5-(3-trifluoromethyl)phenoxy)quinolin-8-yl)pentane-1,4-diamine
1,4-pentanediamine, n4-(2,6-dimethoxy-4-methyl-5-(3-(trifluoromethyl)phenoxy)-8-quinolinyl)-
n(4)-(2,6-dimethoxy-4-methyl-5-((3-trifluoromethyl)phenoxy)-8-quinolinyl)-1,4-pentanediamine
CHEMBL298470
sb-252263-aab
CHEBI:141487
n(4)-{2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl}pentane-1,4-diamine
4-n-[2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]pentane-1,4-diamine
arakoda
262p8gs9l9 ,
unii-262p8gs9l9
tafenoquine [usan:inn:ban]
tafenoquine (usan)
D10490
SCHEMBL347388
tafenoquine [who-dd]
tafenoquine [inn]
tafenoquine [mi]
tafenoquine [usan]
tafenoquine [mart.]
HY-111529
CS-0042381
AKOS030632170
(+/-)-8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-(3-trifluoromethylphenoxy) quinoline
106635-80-7 (free base)
tafenoquine free base
DB06608
n4-(2,6-dimethoxy-4-methyl-5-(3-(trifluoromethyl)phenoxy)quinolin-8-yl)pentane-1,4-diamine
Q2387553
gtpl9722
EX-A3146
SB16555
FT-0775258
D87160
n4-{2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl}pentane-1,4-diamine
EN300-19754461
DTXSID90869466
wr 238,605
chebi:135752
rac-n(4)-(2,6-dimethoxy-4-methyl-5-(3-(trifluoromethyl)phenoxy)quinolin-8-yl)pentane-1,4-diamine
p01ba07
tafenoquine (mart.)
tafenoquina
tafenoquinum

Research Excerpts

Overview

Tafenoquine is an effective prophylactic drug against all parasite life cycle stages and all malaria species that infect humans. It is a single-dose (300 mg) therapy for Plasmodium vivax relapse prevention, when co-administered with 3-days of chloroquine or other blood schizonticide.

ExcerptReferenceRelevance
"Tafenoquine is a long-acting 8-aminoquinoline approved for antimalarial prophylaxis for ≤6 months. "( Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 12-month, randomized, double-blind, placebo-controlled trial.
Chen, FK; Dow, G; Garver Baldwin, LS; Gonzalez, V; Martidis, A; Novitt-Moreno, A; Ransom, J; Read, LT; Reid, M; Scott, CB; Smith, B; Zottig, VE,
)
1.88
"Tafenoquine is an effective prophylactic drug against all parasite life cycle stages and all malaria species that infect humans."( Army Antimalarial Drug Development: An Advanced Development Case Study for Tafenoquine.
Carr, KA; Clarke, JG; Kreishman-Deitrick, M; Shmuklarsky, MJ; Zottig, VE, 2020
)
1.51
"Tafenoquine is an 8-aminoquinoline anti-malarial drug recently approved as a single-dose (300 mg) therapy for Plasmodium vivax relapse prevention, when co-administered with 3-days of chloroquine or other blood schizonticide. "( Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review.
Chalon, S; Duparc, S; Miller, S; Richardson, N; Toovey, S, 2020
)
2.27
"Tafenoquine (TQ) is a new alternative to PQ with a longer half-life and can be used as a single-dose treatment."( Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.
Fernando, D; Rajapakse, S; Rodrigo, C, 2020
)
2.72
"Tafenoquine is a new prophylactic antimalarial drug. "( Tafenoquine for malaria prophylaxis in adults: An integrated safety analysis.
Dow, G; Novitt-Moreno, A; Ransom, J; Read, LT; Smith, B; Toovey, S,
)
3.02
"Tafenoquine is a new drug for malaria prevention. "( Tafenoquine is not neurotoxic following supertherapeutic dosing in rats.
Brown, T; Dow, GS; Reid, M; Smith, B; Toovey, S,
)
3.02
"Tafenoquine (TQ) is an 8-aminoquinoline anti-malarial being developed for malaria prophylaxis. "( The blood schizonticidal activity of tafenoquine makes an essential contribution to its prophylactic efficacy in nonimmune subjects at the intended dose (200 mg).
Dow, G; Smith, B, 2017
)
2.17
"Tafenoquine is an investigational 8-aminoquinoline for the prevention of Plasmodium vivax relapse. "( A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria.
Buathong, N; Euswas, A; Fukuda, MM; Green, JA; Ittiverakul, M; Krudsood, S; Miller, RS; Mohamed, K; Noedl, H; Ohrt, C; Sriwichai, S; Warrasak, S, 2017
)
2.11
"Tafenoquine (TQ) is an 8-aminoquinoline under development for preventing Plasmodium vivax malaria relapse."( Application of the Stable Isotope Label Approach in Clinical Development-Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine, a Long Half-life Compound.
Casillas, L; Duparc, S; Ernest, T; Goyal, N; Koh, GCKW; Mohamed, K; Rolfe, K; Sahota, S; Taylor, M, 2018
)
1.4
"Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P."( Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.
Abdissa, A; Abebe, C; Angus, B; Batista Pereira, D; Beck, HP; Brand, F; Breton, JJ; Brito, MAM; Buathong, N; Casapía, M; Chuquiyauri, R; Clover, DD; Costa, MRF; Diro, E; Duparc, S; Espino, FEJ; Fletcher, K; Getie, S; Green, JA; Hardaker, E; Jones, SW; Kellam, LM; Kleim, JP; Koh, GCKW; Krudsood, S; Lacerda, MVG; Llanos-Cuentas, A; Lon, C; Mia, RZ; Mohamed, K; Mohammed, R; Monteiro, WM; Noedl, H; Rousell, VM; Saunders, DL; Tada, MS; Ugwuegbulam, CO; Val, F; Wubie, KM; Yilma, D; Zeynudin, A, 2019
)
1.61
"Tafenoquine (TQ) is an 8-aminoquinoline (8AQ) that has been tested in several Phase II and Phase III clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. "( Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds.
Bennett, JW; Careagabarja, J; Caridha, D; Deye, G; Dhammika Nanayakkara, NP; Hickman, M; Li, Q; Marcsisin, SR; McNulty, R; Melendez, V; Pybus, BS; Read, L; Reichard, GA; Roncal, N; Sciotti, RJ; Smith, B; Sousa, JC; Walker, LA; Zeng, Q; Zottig, VE, 2014
)
3.29
"Tafenoquine is a new anti-malarial drug in development; the pure drug substance has an asthma hazard index of zero and previously was not known to be a respiratory sensitizing agent."( Occupational asthma from tafenoquine in the pharmaceutical industry: implications for QSAR.
Agius, R; Cannon, J; Cullinan, P; Fitzgerald, B; Jiwany, A; Seed, M, 2015
)
1.44
"Tafenoquine is a new alternative with a longer half-life."( Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.
Fernando, SD; Rajapakse, S; Rodrigo, C, 2015
)
2.58
"Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III."( The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.
Carvalho, L; Gamarro, F; Manzano, JI; Martínez-García, M; Pérez-Victoria, I; Pérez-Victoria, JM; Yardley, V, 2015
)
1.44
"Tafenoquine is a long half-life primaquine analog being developed for malaria prophylaxis. "( Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries.
Dow, GS; Hetzell, B; Lin, G; Liu, J; McCarthy, WF; Smith, B; Tang, D; Thieling, S, 2015
)
2.11
"Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. "( Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta).
Cozens, S; Dow, GS; Gettayacamin, M; Hansukjariya, P; Imerbsin, R; Kenworthy, D; Komcharoen, S; Kyle, D; Milhous, W; Miller, A; Ohrt, C; Sattabongkot, J; Veazey, J, 2011
)
2.1
"Tafenoquine is a new promising antimalarial drug for prophylaxis and treatment."( Determination of tafenoquine in dried blood spots and plasma using LC and fluorescence detection.
Bergqvist, Y; Lindegardh, N; Römsing, S, 2011
)
1.43
"Tafenoquine appears to be a promising candidate for treating multidrug-resistant falciparum malaria, especially in combination with artemisinin derivatives."( In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum.
Noedl, H; Ramharter, M; Thimasarn, K; Wernsdorfer, G; Wernsdorfer, WH; Wiedermann, G, 2002
)
1.35
"Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. "( A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum.
Adjuik, M; Baird, JK; Binka, FN; Franke, ED; Fryauff, DJ; Hale, BR; Hoffman, SL; Horton, J; Koram, KA; Nkrumah, F; Oduro, AR; Owusu-Agyei, S; Prescott, WR; Ritchie, TL, 2003
)
2
"Tafenoquine is an 8-aminoquinoline developed as a more effective replacement for primaquine. "( Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse.
Brewer, TG; Heppner, DG; Krudsood, S; Looareesuwan, S; Phumratanaprapin, W; Silachamroon, U; Siriyanonda, D; Tang, DB; Walsh, DS; Wilairatana, P, 2004
)
2.04
"Tafenoquine is an 8-aminoquiniline related to primaquine with pre-clinical activity against a range of malaria species. "( Treatment of acute vivax malaria with tafenoquine.
Kitchener, S; Nasveld, P, 2005
)
2.04
"Tafenoquine is an 8-aminoquinoline antimalarial that is presently under development."( Tafenoquine: a promising new antimalarial agent.
Crockett, M; Kain, KC, 2007
)
2.5
"Tafenoquine is an analogue of primaquine with an improved therapeutic and safety profile. "( Malaria chemoprophylaxis with tafenoquine: a randomised study.
Borrmann, S; Dangelmaier, O; Faucher, JF; Horton, J; Kremsner, PG; Lell, B; Missinou, MA, 2000
)
2.04
"Tafenoquine is an analogue of primaquine that is more potent than the parent drug."( Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that may be available in the future.
Kain, KC; Keystone, JS; Shanks, GD, 2001
)
1.03

Effects

Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen.

ExcerptReferenceRelevance
"Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen."( A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria.
Buathong, N; Euswas, A; Fukuda, MM; Green, JA; Ittiverakul, M; Krudsood, S; Miller, RS; Mohamed, K; Noedl, H; Ohrt, C; Sriwichai, S; Warrasak, S, 2017
)
1.39
"Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen."( A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria.
Buathong, N; Euswas, A; Fukuda, MM; Green, JA; Ittiverakul, M; Krudsood, S; Miller, RS; Mohamed, K; Noedl, H; Ohrt, C; Sriwichai, S; Warrasak, S, 2017
)
1.39
"Tafenoquine has been recently registered for the prevention of relapse in Plasmodium vivax malaria."( Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.
Ackert, J; Barañano, DE; Berni, A; Coleman, H; Duparc, S; El-Harazi, S; Gevorkyan, H; Green, JA; Hardaker, E; Hussaini, A; Jones, SW; Kelly, DS; Koh, GCKW; Mohamed, K; Patel, J; Rasmussen, S; Sergott, RC; Slakter, JS; Thompson, JT; Tonkyn, J; Warren, KA; Wolstenholme, A; Yuan, A, 2019
)
2.18

Treatment

ExcerptReferenceRelevance
"The tafenoquine-treated subject had this abnormality at baseline, and was enrolled in error."( Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.
Ackert, J; Barañano, DE; Berni, A; Coleman, H; Duparc, S; El-Harazi, S; Gevorkyan, H; Green, JA; Hardaker, E; Hussaini, A; Jones, SW; Kelly, DS; Koh, GCKW; Mohamed, K; Patel, J; Rasmussen, S; Sergott, RC; Slakter, JS; Thompson, JT; Tonkyn, J; Warren, KA; Wolstenholme, A; Yuan, A, 2019
)
1.22

Toxicity

Treatment-related adverse events for the two groups were similar. Adverse events (AE) were comparable in frequency and severity between tafenoquine and comparator arms. The risk of neuropsychiatric adverse events (NPAEs) with single-dose tafinoquine (300 mg) in combination with chloroquine to achieve P.

ExcerptReferenceRelevance
") challenge with a 2 x LD50 dose (5."( Comparison of methemoglobin formers in protection against the toxic effects of cyanide.
Baskin, SI; Fricke, RF; Scharf, BA, 1992
)
0.28
" Treatment-related adverse events for the two groups were similar (tafenoquine, 13."( Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
Brennan, L; Edstein, MD; Harris, IE; Kerr, C; Kitchener, SJ; Leggat, PA; Nasveld, PE; Ohrt, C; Pickford, P; Prescott, W; Reid, M, 2010
)
0.83
" vivax relapse prevention, nervous system adverse events, mainly headache and dizziness, occurred in 11."( Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review.
Chalon, S; Duparc, S; Miller, S; Richardson, N; Toovey, S, 2020
)
0.83
" Adverse events (AE) were comparable in frequency and severity between tafenoquine and comparator arms."( Efficacy and safety of tafenoquine for malaria chemoprophylaxis (1998-2020): A systematic review and meta-analysis.
Baird, JK; Grobusch, MP; Gültekin, N; Maier, JD; Schlagenhauf, P; Siegfried, S; Stanga, Z,
)
0.68
" Our safety analysis is limited by heterogenous methods of adverse events reporting."( Efficacy and safety of tafenoquine for malaria chemoprophylaxis (1998-2020): A systematic review and meta-analysis.
Baird, JK; Grobusch, MP; Gültekin, N; Maier, JD; Schlagenhauf, P; Siegfried, S; Stanga, Z,
)
0.44
" Safety assessments included ophthalmic changes, general and neuropsychiatric adverse events (AEs), and laboratory value changes."( Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 12-month, randomized, double-blind, placebo-controlled trial.
Chen, FK; Dow, G; Garver Baldwin, LS; Gonzalez, V; Martidis, A; Novitt-Moreno, A; Ransom, J; Read, LT; Reid, M; Scott, CB; Smith, B; Zottig, VE,
)
0.44
" Adverse events over the first 28 days were reported in 27 (54%) of 50 patients treated with dihydroartemisinin-piperaquine alone, 29 (58%) of 50 patients treated with tafenoquine plus dihydroartemisinin-piperaquine, and 22 (44%) of 50 patients treated with primaquine plus dihydroartemisinin-piperaquine."( Tafenoquine co-administered with dihydroartemisinin-piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study.
Baird, JK; Berni, A; Budiman, W; Cedar, E; Chand, K; Crenna-Darusallam, C; Duparc, S; Ekawati, LL; Elyazar, I; Fernando, D; Fletcher, K; Goyal, N; Green, JA; Instiaty, I; Jones, S; Kleim, JP; Lardo, S; Martin, A; Noviyanti, R; Prasetya, CB; Rolfe, K; Santy, YW; Satyagraha, AW; Sharma, H; Soebandrio, A; Subekti, D; Sutanto, I; Tan, LK; Taylor, M, 2023
)
2.55

Pharmacokinetics

The pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether, and dihydroartemisinin were determined by using noncompartmental methods. The experiments were conducted in mice with different CYP 2D metabolism statuses.

ExcerptReferenceRelevance
" A two-compartment pharmacokinetic model, linked to a sigmoid Emax pharmacodynamic model, was developed to predict the MHb levels after administration of 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-[(3- trifluoromethyl)phenoxy] quinoline succinate (WR 238605 succinate), a primaquine analogue."( Simultaneous modeling of the pharmacokinetics and methemoglobin pharmacodynamics of an 8-aminoquinoline candidate antimalarial (WR 238605).
Brueckner, RP; Fleckenstein, L, 1991
)
0.28
" WR 238605 has a long absorption phase and is slowly metabolized, with a tmax of 12 hr and an elimination half-life of 14 days."( First-time-in-humans safety and pharmacokinetics of WR 238605, a new antimalarial.
Brueckner, RP; Lasseter, KC; Lin, ET; Schuster, BG, 1998
)
0.3
" Population pharmacokinetic modelling was performed using NONMEM."( Population pharmacokinetics of the new antimalarial agent tafenoquine in Thai soldiers.
Brewer, TG; Charles, BG; Eamsila, C; Edstein, MD; Kocisko, DA; Walsh, DS, 2001
)
0.55
" The interoccasion variability in CL/F was 18%, and the mean elimination half-life was 12."( Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
Charles, BG; Edstein, MD; Harris, IE; Miller, AK; Nasveld, PE; Reid, MG, 2007
)
0.63
" Coadministration therapy was evaluated for a pharmacokinetic interaction and for pharmacodynamic, safety and tolerability characteristics."( Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects.
Baptiste-Brown, S; Beelen, AP; Duparc, S; Griffith, S; Harrell, E; Hughes, A; Kleim, JP; Miller, AK; Möhrle, JJ; Ohrt, C; Stinnett, S; Webster, A; Ye, L, 2013
)
0.62
" Blood samples for pharmacokinetic and pharmacodynamic analyses and safety data, including electrocardiograms, were collected for 56 days."( Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects.
Baptiste-Brown, S; Beelen, AP; Duparc, S; Griffith, S; Harrell, E; Hughes, A; Kleim, JP; Miller, AK; Möhrle, JJ; Ohrt, C; Stinnett, S; Webster, A; Ye, L, 2013
)
0.62
"The coadministration of CQ + TQ had no effect on TQ AUC0-t , AUC0-∞ , Tmax or t1/2 ."( Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects.
Baptiste-Brown, S; Beelen, AP; Duparc, S; Griffith, S; Harrell, E; Hughes, A; Kleim, JP; Miller, AK; Möhrle, JJ; Ohrt, C; Stinnett, S; Webster, A; Ye, L, 2013
)
0.62
" Comparative pharmacokinetic (PK) and liver distribution studies of oral and intravenous PQ and TQ were also performed."( Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections.
Caridha, D; Hickman, M; Li, Q; Melendez, V; O'Neil, M; Pybus, B; Xie, L; Zeng, Q; Zhang, J, 2014
)
0.63
" The elimination half-life of oral TQ in mice was 28 times longer than PQ, and the liver tissue distribution of TQ revealed an AUC that was 188-fold higher than PQ."( Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections.
Caridha, D; Hickman, M; Li, Q; Melendez, V; O'Neil, M; Pybus, B; Xie, L; Zeng, Q; Zhang, J, 2014
)
0.63
" In this study, a series of tafenoquine pharmacokinetic experiments were conducted in mice with different CYP 2D metabolism statuses, including wild-type (WT) (reflecting extensive metabolizers for CYP 2D6 substrates) and CYPmouse 2D knockout (KO) (reflecting poor metabolizers for CYP 2D6 substrates) mice."( Differential cytochrome P450 2D metabolism alters tafenoquine pharmacokinetics.
Duan, D; Li, Q; Marcsisin, SR; Nanayakkara, NP; Nolan, CK; Paris, RM; Potter, BM; Pybus, BS; Read, LT; Reichard, GA; Sciotti, RJ; Smith, B; Smith, PL; Sousa, JC; Tekwani, BL; Vuong, C; Walker, LA; Xie, LH; Zhang, J; Zhang, P; Zottig, VE, 2015
)
0.96
" The pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether, and dihydroartemisinin were determined by using noncompartmental methods."( Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects.
Bouhired, S; Duparc, S; Goyal, N; Green, JA; Hussaini, A; Jones, SW; Koh, GC; Kostov, I; Mohamed, K; Taylor, M; Wolstenholm, A, 2016
)
0.98
"This open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 study enrolled children (2-15 years) who weighed 5 kg or more, with glucose-6-phosphate dehydrogenase activity more than 70% of the local population median, and P vivax malaria infection, from three community health centres in Vietnam and one in Colombia."( Tafenoquine exposure assessment, safety, and relapse prevention efficacy in children with Plasmodium vivax malaria: open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 trial.
Breton, JJ; Chau, NH; Duparc, S; Ernest, TB; Goyal, N; Green, JA; Hien, TT; Hoa, NT; Jones, SW; Martin, A; Mohamed, K; Rolfe, K; Rousell, VM; Sharma, H; Tan, LK; Taylor, M; Vélez, ID, 2022
)
2.16

Compound-Compound Interactions

Study was conducted to assess the in vitro blood schizontocidal activity of tafenoquine, the most advanced candidate drug of the 8-aminoquinolines. Study measured the inhibition of schizont maturation.

ExcerptReferenceRelevance
" This study was conducted to assess the in vitro blood schizontocidal activity of tafenoquine, the most advanced candidate drug of the 8-aminoquinolines, and of its 1:1 combination with artemisinin in fresh isolates of Plasmodium falciparum in an area with multi-drug resistance, measuring the inhibition of schizont maturation."( In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum.
Noedl, H; Ramharter, M; Thimasarn, K; Wernsdorfer, G; Wernsdorfer, WH; Wiedermann, G, 2002
)
0.86
" The ST provided evidence for the contention that a combination with PQ slowed the selection of resistance to CQ or MEF; it has been shown previously that synergism exists between CQ and either PQ or TAF in rodent malaria."( The chemotherapy of rodent malaria. LXI. Drug combinations to impede the selection of drug resistance, part 4: the potential role of 8-aminoquinolines.
Peters, W; Robinson, BL; Stewart, LB, 2003
)
0.32
" We aimed to establish the efficacy and safety of three single low doses of tafenoquine in combination with dihydroartemisinin-piperaquine for reducing gametocyte density and transmission to mosquitoes."( Single low-dose tafenoquine combined with dihydroartemisinin-piperaquine to reduce Plasmodium falciparum transmission in Ouelessebougou, Mali: a phase 2, single-blind, randomised clinical trial.
Attaher, O; Bousema, T; Bradley, J; Diallo, M; Dicko, A; Dicko, OM; Drakeley, C; Issiaka, D; Keita, S; Lanke, K; Maguiraga, SO; Mahamar, A; McCall, MBB; Niambele, SM; Sacko, A; Samake, S; Sanogo, K; Sinaba, Y; Smit, MJ; Stone, W; Ter Heine, R; Traore, SF, 2022
)
1.3

Bioavailability

ExcerptReferenceRelevance
" The results of a pilot study assessing the relative oral bioavailability of two different salt forms of the new antimalarial in dogs show the usefulness of the method for animal and human pharmacokinetic studies."( Rapid and sensitive quantitative analysis of the new antimalarial N4-[2,6-dimethoxy-4-methyl-5-[(3-trifluoromethyl)phenoxy]-8- quinolinyl]-1,4-pentanediamine in plasma by liquid chromatography and electrochemical detection.
Karle, JM; Olmeda, R, 1988
)
0.27
"Tafenoquine (TQ), a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals."( Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice.
deKock, C; Dube, A; Gibhard, L; Hayeshi, R; Kalombo, L; Melariri, P; Nkuna, P; Ogutu, B; Smith, P; Swai, H; Wiesner, L, 2015
)
2.13

Dosage Studied

Tafenoquine's long half-life allows a single dose to achieve radical cure. Weekly dosing for chemoprophylaxis to provide an exciting therapeutic option for patient care.

ExcerptRelevanceReference
" The model was then validated in three additional dogs given three different dosing regimens."( Simultaneous modeling of the pharmacokinetics and methemoglobin pharmacodynamics of an 8-aminoquinoline candidate antimalarial (WR 238605).
Brueckner, RP; Fleckenstein, L, 1991
)
0.28
" A total dose of 3 mg/kg of WR 238605 given at a dosage of 1 mg/kg/day for three days cleared patent parasites in all eight monkeys but recrudescence of parasitemia occurred 15-25 days after initiation of treatment."( WR 238605, chloroquine, and their combinations as blood schizonticides against a chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys.
Cooper, RD; Kyle, DE; Nuzum, EO; Obaldia, N; Rieckmann, KH; Rossan, RN; Shanks, GD, 1997
)
0.3
" Its long half-life allows for infrequent dosing (currently tested at 200 mg base/week), and its effect on parasites at the liver stage may allow for drug discontinuation at the time of departure from the area of endemicity."( Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that may be available in the future.
Kain, KC; Keystone, JS; Shanks, GD, 2001
)
0.31
" A positive linear association between weight and both CL/F and V/F was found, but this had insufficient impact to warrant dosage adjustments."( Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
Charles, BG; Edstein, MD; Harris, IE; Miller, AK; Nasveld, PE; Reid, MG, 2007
)
0.63
" The (-)-enantiomer NPC1161B was found to be more active (by severalfold, depending on the dosing regimen) than the (+)-enantiomer NPC1161A in all of these murine models."( Antiparasitic activities and toxicities of individual enantiomers of the 8-aminoquinoline 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate.
Ager, AL; Bartlett, MS; Croft, SL; Khan, IA; McChesney, JD; Nanayakkara, NP; Walker, LA; Yardley, V, 2008
)
0.35
" The much shorter dosing regimen of tafenoquine should increase compliance, which is often suboptimal with primaquine after leaving an endemic area."( The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific.
Edstein, MD; Elmes, NJ; Kitchener, SJ; Kocisko, DA; Nasveld, PE, 2008
)
0.86
" Representative compounds 8e and 9c showed good causal prophylactic activity in Rhesus monkeys dosed 30 mg/kg/day for 3 consecutive days by IM, delayed patency for 19-21 days and 54-86 days, respectively, as compared to the untreated control."( New imidazolidinedione derivatives as antimalarial agents.
Kozar, MP; Lin, AJ; Luong, T; Melendez, V; Sathunuru, R; Zhang, L, 2011
)
0.37
"NPC-1161B and TQ exhibited no anti-malarial activity in CYP 2D knock-out mice when dosed at their ED100 values (1 mg/kg and 3 mg/kg, respectively) established in WT mice."( Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds.
Bennett, JW; Careagabarja, J; Caridha, D; Deye, G; Dhammika Nanayakkara, NP; Hickman, M; Li, Q; Marcsisin, SR; McNulty, R; Melendez, V; Pybus, BS; Read, L; Reichard, GA; Roncal, N; Sciotti, RJ; Smith, B; Sousa, JC; Walker, LA; Zeng, Q; Zottig, VE, 2014
)
1.85
" Tafenoquine dose comparisonsThree of the included trials compared eight different dosing regimens."( Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.
Fernando, SD; Rajapakse, S; Rodrigo, C, 2015
)
2.77
" berghei sporozoite murine challenge model was utilized to directly compare causal prophylactic and erythrocytic activity (asexual and sexual parasite stages) dose-response relationships in C57BL/6 wild-type (WT) mice and subsequently compare the erythrocytic activity of PQ and TQ in WT and CYP2D knock-out (KO) mice."( Cytochrome P450 2D-mediated metabolism is not necessary for tafenoquine and primaquine to eradicate the erythrocytic stages of Plasmodium berghei.
Berman, J; Caridha, D; Dickson, SP; Hickman, M; Lee, PJ; Li, Q; Marcsisin, SR; Milner, EE; Read, LT; Roncal, N; Vesely, BA; Xie, LH; Zhang, J; Zhang, P, 2016
)
0.68
" The deficiencies of present agents are parasite resistance to chloroquine, neuropsychiatric liability of mefloquine, the need for daily dosing for atovaquone-proguanil, and daily dosing plus adverse reactions for doxycycline."( Approval of Tafenoquine for Malaria Chemoprophylaxis.
Berman, JD, 2019
)
0.89
" vivax, and it can be dosed weekly to prevent malaria."( Tafenoquine: the new kid on the block.
Chen, V; Daily, JP, 2019
)
1.96
"Tafenoquine's long half-life allows a single dose to achieve radical cure, and weekly dosing for chemoprophylaxis to provide an exciting therapeutic option for patient care and as a new weapon for malaria control/eradication programs."( Tafenoquine: the new kid on the block.
Chen, V; Daily, JP, 2019
)
3.4
" The development of tafenoquine has been conducted over many years, using various dosing regimens in diverse populations."( Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review.
Chalon, S; Duparc, S; Miller, S; Richardson, N; Toovey, S, 2020
)
1.15
" We aimed to determine appropriate oral tafenoquine paediatric dosing regimens, including a dispersible formulation, and evaluated tafenoquine efficacy and safety in children infected with P vivax."( Tafenoquine exposure assessment, safety, and relapse prevention efficacy in children with Plasmodium vivax malaria: open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 trial.
Breton, JJ; Chau, NH; Duparc, S; Ernest, TB; Goyal, N; Green, JA; Hien, TT; Hoa, NT; Jones, SW; Martin, A; Mohamed, K; Rolfe, K; Rousell, VM; Sharma, H; Tan, LK; Taylor, M; Vélez, ID, 2022
)
2.43
" Dosing groups were assigned by body weight, predicted to achieve similar median exposures as the approved 300 mg dose for adults: patients who weighed 5 kg or more to 10 kg received 50 mg, those who weighed more than 10 to 20 kg received 100 or 150 mg, those who weighed more than 20 to 35 kg received 200 mg, and patients who weighed more than 35 kg received 300 mg."( Tafenoquine exposure assessment, safety, and relapse prevention efficacy in children with Plasmodium vivax malaria: open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 trial.
Breton, JJ; Chau, NH; Duparc, S; Ernest, TB; Goyal, N; Green, JA; Hien, TT; Hoa, NT; Jones, SW; Martin, A; Mohamed, K; Rolfe, K; Rousell, VM; Sharma, H; Tan, LK; Taylor, M; Vélez, ID, 2022
)
2.16
" Participants were randomly assigned (1:1:1:1) to standard treatment with dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus a single dose of tafenoquine (in solution) at a final dosage of 0·42 mg/kg, 0·83 mg/kg, or 1·66 mg/kg."( Single low-dose tafenoquine combined with dihydroartemisinin-piperaquine to reduce Plasmodium falciparum transmission in Ouelessebougou, Mali: a phase 2, single-blind, randomised clinical trial.
Attaher, O; Bousema, T; Bradley, J; Diallo, M; Dicko, A; Dicko, OM; Drakeley, C; Issiaka, D; Keita, S; Lanke, K; Maguiraga, SO; Mahamar, A; McCall, MBB; Niambele, SM; Sacko, A; Samake, S; Sanogo, K; Sinaba, Y; Smit, MJ; Stone, W; Ter Heine, R; Traore, SF, 2022
)
1.26
" Parasite regrowth occurred after dosing with 200 mg (3/3 participants) and 300 mg (3/4 participants) but not after 400 mg or 600 mg."( Characterizing the Blood-Stage Antimalarial Activity of Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum.
Abd-Rahman, AN; Barber, BE; Birrell, GW; Edstein, MD; Leelasena, I; Llewellyn, S; Marquart, L; McCarthy, JS; Moehrle, JJ; Potter, AJ; Sahai, N; Shanks, GD; Webster, R; Wesche, D, 2023
)
1.16
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (5)

ClassDescription
(trifluoromethyl)benzenesAn organofluorine compound that is (trifluoromethyl)benzene and derivatives arising from substitution of one or more of the phenyl hydrogens.
aminoquinolineAny member of the class of quinolines in which the quinoline skeleton is substituted by one or more amino or substituted-amino groups.
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
primary amino compoundA compound formally derived from ammonia by replacing one hydrogen atom by an organyl group.
secondary amino compoundA compound formally derived from ammonia by replacing two hydrogen atoms by organyl groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (144)

Assay IDTitleYearJournalArticle
AID341780Clast in po dosed human receiving 600 mg cumulative dose and reporting drug-associated vomiting and/or nausea reported on day 3 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID554041Therapeutic index, ratio of IC50 for mouse RAW264.7 cells to IC50 for mefloquine-susceptible Plasmodium falciparum CDC Indochina 3 W22011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID184458Acute toxicity administered intraperitoneally was determined in female rats1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID341802Apparent volume of distribution with respect to bioavailability in po dosed human at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID586932Drug uptake in promastigotes of tafenoquine-resistant promastigotes of Leishmania major R4 assessed per mg of protein at 5 uM after 15 mins by spectrofluorometric technique2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID125819Radical curative antimalarial activity against Plasmodium cynomolgi infected Rhesus monkeys (Macaca mulatta) at 0.316 mg/kg/day peroral dose over 7 days; Cured 4 of 41989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID256133Prophylactic activity in infected mouse at 40 mg/kg peroral administration, expressed as no of organisms survived; Total organisms= 52005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
AID586928Drug uptake in wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin at 2 uM after 5 mins by spectrofluorometric technique2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID117459Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 640 mg/kg perorally; 4 cured and in 1 toxic1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID1775004Toxicity against non-human primate hepatocytes infected with liver stage Plasmodium cynomolgi B incubated for 4 days starting on day 4 post-sporozoite inoculation
AID620052Antimalarial activity against sporozoites stage of Plasmodium cynomolgi infected in Rhesus monkey assessed as delay in patency at 0.316 mg/kg/day, po administered one day before infection, on day of infection and one day post infection2011Journal of medicinal chemistry, Oct-13, Volume: 54, Issue:19
Antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives.
AID341793Apparent volume of distribution with respect to the bioavailability in po dosed human receiving 1000 mg cumulative dose and reporting drug-associated depression on day 24 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID774663Antimalarial activity against early (1 to 3) gametocytic stage of Plasmodium falciparum after 72 hrs by image-based HTS assay2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Approaches to protozoan drug discovery: phenotypic screening.
AID509083Toxicity in patient with malaria assessed as incidence of upper respiratory tract infection at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID341783Clast in po dosed human receiving 1000 mg cumulative dose and reporting drug-associated depression reported on day 24 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID554033Half life in human microsomes by LC-MS/MS analysis2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID117445Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 20 mg/kg perorally; 3 cured1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID341804Tmax in fasted human2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509080Toxicity in patient with malaria assessed as incidence of fungal dermatitis at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID586923Resistant index, ratio of EC50 for tafenoquine-resistant promastigotes of Leishmania major R4 to EC50 for promastigotes of Leishmania major MHOM/JL/80/Friedlin2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID117439Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 160 mg/kg perorally; 5 cured1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID554034Half life in mouse microsomes by LC-MS/MS analysis2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID117301Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 10 mg/kg perorally; Inactive1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID341785Apparent clearance with respect to the bioavailability po dosed human receiving 200 mg cumulative dose and reporting drug-associated insomnia reported on day 1 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509302Toxicity in patient with malaria assessed as incidence of paroniria at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID554035Prophylactic antimalarial activity against Plasmodium berghei infected Exoerythrocytic mouse model2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID341806Trough concentration in po dosed human at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months after 4 weeks2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID587017Induction of acidification in tafenoquine-resistant promastigotes of Leishmania major revert R4 assessed as decrease of pH at 5 uM after 30 mins2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID509298Toxicity in patient with malaria assessed as incidence of decrease in hematocrit at 250 mg, perorally for 3 days and weekly 250 mg, perorally maintenance dose for 26 +/- 4 weeks relative to baseline2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID256129Prophylactic activity in infected mouse at 5 mg/kg peroral administration, expressed as no of organisms survived; Total organisms= 52005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
AID587013Drug uptake in promastigotes of tafenoquine-resistant promastigotes of Leishmania major R4 assessed per mg of protein at 5 uM after 15 mins by spectrofluorometric technique in presence of sodium chloride2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID574858Antiplasmodial activity against Plasmodium cynomolgi sporozoites infected in Rhesus monkey assessed as duration for detection of parasites in blood at 0.316 mg/kg/day, po administered for three consecutive days before infection (Rvb = 8 days)2011Bioorganic & medicinal chemistry, Feb-15, Volume: 19, Issue:4
New imidazolidinedione derivatives as antimalarial agents.
AID341801Apparent clearance with respect to bioavailability in po dosed human at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509313Toxicity in patient with malaria assessed as incidence of vertigo at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID330908Binding affinity to human serum albumin by circular dichroism and UV/VIS spectroscopic method2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID117463Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 80 mg/kg perorally; 5 cured1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID230860Molar primaquine index is ratio of ED50 of Compound by ED50 of primaquine in rhesus monkey1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID586926Induction of acidification in wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin assessed as decrease of pH at 5 uM after 30 mins2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID574869Antiplasmodial activity against Plasmodium cynomolgi sporozoites infected in Rhesus monkey assessed as delay in detection of parasites in blood at 0.316 mg/kg/day, po administered for three consecutive days before infection2011Bioorganic & medicinal chemistry, Feb-15, Volume: 19, Issue:4
New imidazolidinedione derivatives as antimalarial agents.
AID586929Drug uptake in promastigotes of tafenoquine-resistant promastigotes of Leishmania major R4 at 2.5 uM after 5 mins by spectrofluorometric technique2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID509088Toxicity in patient with malaria assessed as incidence of abdominal pain at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID341789Apparent volume of distribution with respect to the bioavailability in po dosed human receiving 400 mg cumulative dose and reporting drug-associated diarrhea and/or abdominal pain on day 2 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 62007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID1775002Antiplasmodial activity against liver stage Plasmodium cynomolgi B infected in non-human primate hepatocytes assessed as reduction in liver hypnozoites development incubated for 4 days starting on day 4 post-sporozoite inoculation by radial cure mode anal
AID1775003Toxicity against non-human primate hepatocytes infected with liver stage Plasmodium cynomolgi B incubated for 4 days from sporozoite addition
AID330903Binding affinity to human AAG at 37 degC by induced circular dichroism method2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID125816Radical curative antimalarial activity against Plasmodium cynomolgi infected Rhesus monkeys (Macaca mulatta) at 0.10 mg/kg/day peroral dose over 7 days; cured 2 of 41989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID774658Antimalarial activity against asexual stage of Plasmodium falciparum 3D7 after 72 hrs by image-based HTS assay2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Approaches to protozoan drug discovery: phenotypic screening.
AID509306Toxicity in patient with malaria assessed as incidence of agitation at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID554039Cytotoxicity against mouse RAW264.7 cells after 24 hrs by MTT assay2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID509096Toxicity in patient with malaria assessed as incidence of abnormal retinal fluorescein at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID509305Toxicity in patient with malaria assessed as incidence of euphoria at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID117456Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 5 mg/kg perorally; Inactive1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID341796Half life po dosed human receiving 200 mg cumulative dose and reporting drug-associated insomnia on day 1 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID341794Apparent volume of distribution with respect to the bioavailability in po dosed human receiving 600 mg cumulative dose and reporting drug-associated vomiting and/or nausea on day 3 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID772517Antimalarial activity against sporozoite stage of Plasmodium yoelii assessed as invasion of human HepG2 cells expressing CD81 incubated for 2 hrs prior to inoculation measured after 1 hr by immunofluorescence assay in presence of penicillin/streptomycin2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Using genetic methods to define the targets of compounds with antimalarial activity.
AID341798Half life po dosed human receiving 1000 mg cumulative dose and reporting drug-associated abdominal pain on day 20 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID586934Drug uptake in wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin assessed per mg of protein at 5 uM after 15 mins by spectrofluorometric technique in presence of sodium chloride2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID509081Toxicity in patient with malaria assessed as incidence of rash at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID341784Apparent clearance with respect to the bioavailability po dosed human receiving 400 mg cumulative dose and reporting drug-associated diarrhea and/or abdominal pain on day 2 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID587020Induction of acidification in tafenoquine-resistant promastigotes of Leishmania major revert R4 assessed as decrease of pH at 20 mM after 30 mins2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID330907Displacement of quinaldine red from human AAG by fluorescence method2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID509094Toxicity in patient with malaria assessed as incidence of pigmentation of retinal epithelium at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID509085Toxicity in patient with malaria assessed as incidence of back pain at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID509087Toxicity in patient with malaria assessed as incidence of vomiting at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID341799Half life po dosed human receiving 1000 mg cumulative dose and reporting drug-associated depression on day 24 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID586931Drug uptake in wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin assessed per mg of protein at 5 uM after 15 mins by spectrofluorometric technique2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID509079Toxicity in patient with malaria assessed as incidence of headache at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID586925Antileishmanial activity against wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin assessed as inhibition of parasite growth after 72 hrs by MTT assay2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID509312Toxicity in patient with malaria assessed as incidence of somnolence at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID184597Acute toxicity administered orally was determined in female rats1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID509310Toxicity in patient with malaria assessed as incidence of dizziness at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID587018Induction of acidification in wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin assessed as decrease of pH at 20 mM after 30 mins2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID125812Radical curative antimalarial activity against Plasmodium cynomolgi infected Rhesus monkeys (Macaca mulatta) at 0.0316 mg/kg/day peroral dose over 7 days; Cured 0 of 21989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID509309Toxicity in patient with malaria assessed as incidence of insomnia at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID117453Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 40 mg/kg perorally; 5 cured1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID509082Toxicity in patient with malaria assessed as incidence of phayngitis at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID586924Antileishmanial activity against tafenoquine-resistant promastigotes of Leishmania major R4 assessed as inhibition of parasite growth after 72 hrs by MTT assay2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID125822Radical curative antimalarial activity against Plasmodium cynomolgi infected Rhesus monkeys (Macaca mulatta) at 1 mg/kg/day peroral dose over 7 days; cured 2 of 21989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID554037Antimalarial activity against mefloquine-resistant Plasmodium falciparum CDC Sierra Leone 1 D6 after 48 hrs by [3H]hypoxanthine uptake assay2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID509089Toxicity in patient with malaria assessed as incidence of nausea at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID341797Half life po dosed human receiving 800 mg cumulative dose and reporting drug-associated hyperesthesia on day 12 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID256128Prophylactic activity in infected mouse at 160 mg/kg peroral administration, expressed as no of organisms survived; Toxicity death2005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
AID587014Drug uptake in promastigotes of tafenoquine-resistant promastigotes of Leishmania major revert R4 assessed per mg of protein at 5 uM after 15 mins by spectrofluorometric technique in presence of sodium chloride2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID341809Trough concentration in po dosed human at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months after 16 weeks2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID1685962Antiplasmodial activity against late stage (IV/V) Plasmodium falciparum NF54 gametocytes transfected with GFP-LUC assessed as growth inhibition incubated for 72 hrs by mitotracker Red-CMXROS dye based fluorescence microscopic analysis2016Journal of medicinal chemistry, 11-10, Volume: 59, Issue:21
Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy.
AID509084Toxicity in patient with malaria assessed as incidence of arthralgia at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID774661Antimalarial activity against late (4 to 5) gametocytic stage of Plasmodium falciparum after 72 hrs by image-based HTS assay2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Approaches to protozoan drug discovery: phenotypic screening.
AID341782Clast in po dosed human receiving 1000 mg cumulative dose and reporting drug-associated abdominal pain on day 20 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509304Toxicity in patient with malaria assessed as incidence of tremor at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID1192800Antimalarial activity against multidrug-resistant Plasmodium falciparum W2 by SYBR green-based assay2015Bioorganic & medicinal chemistry letters, Mar-01, Volume: 25, Issue:5
Synthesis and in vitro evaluation of novel 8-aminoquinoline-pyrazolopyrimidine hybrids as potent antimalarial agents.
AID709185Half life in human plasma2012Journal of medicinal chemistry, Dec-13, Volume: 55, Issue:23
Effects of antimalarial molecules on the gametocyte stage of Plasmodium falciparum: the debate.
AID586930Drug uptake in promastigotes of tafenoquine-resistant promastigotes of Leishmania major revert R4 at 5 uM after 5 mins by spectrofluorometric technique2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID330910Binding affinity to human AAG by fluorescence emission spectra2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID341808Trough concentration in po dosed human at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months after 8 weeks2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID341781Clast in po dosed human receiving 200 mg cumulative dose and reporting drug-associated hyperesthesia on day 12 dosed at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID330906Binding affinity to human AAG at 23 degC by induced circular dichroism method2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID772516Antimalarial activity against mature gametocytic stage of Plasmodium falciparum assessed as inhibition of mature gamete exflagellation at 10 uM incubated for 24 hrs prior to exflagellation induction at 21 degC measured after 20 mins by microscopic analysi2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Using genetic methods to define the targets of compounds with antimalarial activity.
AID509301Toxicity in patient with malaria assessed as incidence of increase in serum creatinine at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID619003Antimalarial activity against Plasmodium cynomolgi infected in rhesus monkey assessed as delay in patency time at 0.316 mg/kg, po administered one day before infection, on day of infection followed by 1 day post infection2011Journal of medicinal chemistry, Jul-14, Volume: 54, Issue:13
Synthesis and antimalarial activity of 2-guanidino-4-oxoimidazoline derivatives.
AID341807Apparent clearance with respect to the bioavailability po dosed human receiving 1000 mg cumulative dose and reporting drug-associated abdominal pain on day 20 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID341800Half life po dosed human receiving 1000 mg cumulative dose and reporting drug-associated vomiting and/or nausea on day 3 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509311Toxicity in patient with malaria assessed as incidence of abnormal dreams at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID509091Toxicity in patient with malaria assessed as incidence of gastroentertis at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID1775000Antiplasmodial activity against liver stage Plasmodium cynomolgi B infected in non-human primate hepatocytes assessed as inhibition of hypnozoite development incubated for 4 days from sporozoite addition by prophylactic assay
AID341803Half life in po dosed human at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID587019Induction of acidification in tafenoquine-resistant promastigotes of Leishmania major R4 assessed as decrease of pH at 20 mM after 30 mins2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID586933Drug uptake in promastigotes of tafenoquine-resistant promastigotes of Leishmania major revert R4 assessed per mg of protein at 5 uM after 15 mins by spectrofluorometric technique2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID184598Acute toxicity administered orally was determined in male rats1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID509307Toxicity in patient with malaria assessed as incidence of anxiety at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID162092Minimal effective concentration inhibiting growth of Pneumocystis carinii was reported.1995Journal of medicinal chemistry, Nov-24, Volume: 38, Issue:24
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.
AID256314In vitro antimalarial activity dosed at 1 mg/kg against exoerythrocytic Plasmodium yoelii in mice (Mus musculus) hepatocytes2005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
AID509297Toxicity in patient with malaria assessed as incidence of decrease in hematocrit at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID509303Toxicity in patient with malaria assessed as incidence of depression at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID341791Apparent volume of distribution with respect to the bioavailability in po dosed human receiving 800 mg cumulative dose and reporting drug-associated hyperesthesia on day 12 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509093Toxicity in patient with malaria assessed as incidence of vortex keratopathy at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID256137Prophylactic activity in infected mouse at 2.5 mg/kg peroral administration, expressed as no of organisms survived; Total organisms= 52005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
AID1775001Antiplasmodial activity against liver stage Plasmodium cynomolgi B infected in non-human primate hepatocytes assessed as reduction in liver schizonts development incubated for 4 days starting on day 4 post-sporozoite inoculation by radial cure mode analys
AID496819Antimicrobial activity against Plasmodium falciparum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID554040Therapeutic index, ratio of IC50 for mouse RAW264.7 cells to IC50 for mefloquine-resistant Plasmodium falciparum CDC Sierra Leone 1 D62011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID341787Apparent clearance with respect to the bioavailability po dosed human receiving 1000 mg cumulative dose and reporting drug-associated depression on day 24 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID587015Effect on ATP synthesis in wild type promastigotes of Leishmania major MHOM/JL/80/Friedlin assessed as decrease of ATP level up to 20 uM after 60 mins by celltiter- glo luminescent assay2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID341788Apparent clearance with respect to the bioavailability in human at 600 mg cumulative dose with vomiting and/or nausea reported on day 3 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months, po2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID341795Half life po dosed human receiving 400 mg cumulative dose and reporting drug-associated diarrhea and/or abdominal pain on day 2 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509289Toxicity in patient with malaria assessed as incidence of amnesia at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID509078Toxicity in patient with malaria assessed as incidence of viral infection at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID587016Effect on ATP synthesis in tafenoquine-resistant promastigotes of Leishmania major R4 assessed as increase of ATP level at up to 20 uM after 60 mins by celltiter- glo luminescent assay2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID553793Toxicity in Beagle dog assessed as increase in methemoglobin level at 6.4 mg/kg/day, po between 7 to 11 days2008Antimicrobial agents and chemotherapy, Jun, Volume: 52, Issue:6
Antiparasitic activities and toxicities of individual enantiomers of the 8-aminoquinoline 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate.
AID341805Tmax in human administered with standard high-fat meal2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509299Toxicity in patient with malaria assessed as incidence of increase in bilirubin at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID256318In vitro antimalarial activity dosed at 10 mg/kg against exoerythrocytic Plasmodium yoelii in mice (Mus musculus) hepatocytes2005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
AID586927Induction of acidification in tafenoquine-resistant promastigotes of Leishmania major R4 assessed as decrease of pH at 5 uM after 30 mins2011Antimicrobial agents and chemotherapy, Mar, Volume: 55, Issue:3
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AID1774999Antiplasmodial activity against liver stage Plasmodium cynomolgi B infected in non-human primate hepatocytes assessed as inhibition of liver schizonts development incubated for 4 days from sporozoite addition by prophylactic assay
AID509086Toxicity in patient with malaria assessed as incidence of musculoskeletal injury at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID117448Suppressive antimalarial activity against Plasmodium berghei in Rane mice (Mus musculus) when administered at 320 mg/kg perorally; 5 cured1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID509308Toxicity in patient with malaria assessed as incidence of abnormal coordination at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID330909Binding affinity to human serum albumin by fluorescence emission spectra2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID184592Acute toxicity administered intraperitoneally was determined in male rats1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.
AID341790Apparent volume of distribution with respect to the bioavailability in po dosed human receiving 400 mg cumulative dose and reporting drug-associated insomnia on day 1 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID509090Toxicity in patient with malaria assessed as incidence of diarrhea at 200 mg, perorally for 3 days and weekly 200 mg, perorally maintenance dose for 26 +/- 4 weeks2010Antimicrobial agents and chemotherapy, Feb, Volume: 54, Issue:2
Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
AID554038Antimalarial activity against mefloquine-susceptible Plasmodium falciparum CDC Indochina 3 W2 after 48 hrs by [3H]hypoxanthine uptake assay2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.
AID341786Apparent clearance with respect to the bioavailability po dosed human receiving 800 mg cumulative dose and reporting drug-associated with hyperesthesia on day 12 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID341792Apparent volume of distribution with respect to the bioavailability in po dosed human receiving 1000 mg cumulative dose and reporting drug-associated abdominal pain on day 20 at 200 mg daily for 3 days followed by weekly dose of 200 mg for 6 months2007Antimicrobial agents and chemotherapy, Aug, Volume: 51, Issue:8
Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects.
AID330911Binding affinity to human serum albumin on sepharose column by affinity chromatography2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.
AID256131Prophylactic activity in infected mouse at 10 mg/kg peroral administration, expressed as no of organisms survived; Total organisms= 52005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (176)

TimeframeStudies, This Drug (%)All Drugs %
pre-19904 (2.27)18.7374
1990's23 (13.07)18.2507
2000's31 (17.61)29.6817
2010's83 (47.16)24.3611
2020's35 (19.89)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 56.42

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index56.42 (24.57)
Research Supply Index5.41 (2.92)
Research Growth Index5.43 (4.65)
Search Engine Demand Index91.23 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (56.42)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials37 (19.89%)5.53%
Reviews31 (16.67%)6.00%
Case Studies2 (1.08%)4.05%
Observational0 (0.00%)0.25%
Other116 (62.37%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (29)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase I Study to Investigate the Hemolytic Potential of Tafenoquine in Healthy Subjects With Glucose-6-phosphate Dehydrogenase Deficiency and the Safety and Tolerability of Tafenoquine in Acute Plasmodium Vivax Malaria Patients With Glucose-6-phosphate [NCT01205178]Phase 1192 participants (Actual)Interventional2009-07-02Completed
Safety, Tolerability and Pharmacokinetics of Tafenoquine After Weekly and Escalating Monthly Doses of Tafenoquine in Healthy Vietnamese Volunteers [NCT05203744]Phase 4200 participants (Anticipated)Interventional2022-05-10Not yet recruiting
A Revised Tafenoquine Dose to Improve Radical Cure for Vivax Malaria - TAfenoquine DOsing REvised [NCT06148792]Phase 31,090 participants (Anticipated)Interventional2024-04-01Not yet recruiting
A Four-arm Trial Comparing Artemether-lumefantrine With or Without Single-dose Primaquine and Sulphadoxine-pyrimethamine/Amodiaquine With or Without Single-dose Tafenoquine to Reduce P. Falciparum Transmission in Mali [NCT05081089]Phase 280 participants (Actual)Interventional2021-10-12Completed
Optimizing the Dose of Tafenoquine for the Radical Cure of Plasmodium Vivax Malaria in Southeast Asia [NCT04704999]Phase 4700 participants (Anticipated)Interventional2023-09-18Not yet recruiting
Single Site, Randomized, Double Blind, Placebo-Controlled Study to Assess the Long-Term Safety of Tafenoquine [NCT03320174]Phase 2600 participants (Actual)Interventional2017-10-05Completed
"A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression (the ACLR8-LR Study)" [NCT05947812]Phase 2148 participants (Anticipated)Interventional2023-08-01Not yet recruiting
Safety, Tolerability, and Pharmacokinetic Study of Concomitant Chloroquine and Tafenoquine in Healthy Volunteers [NCT00871156]Phase 168 participants (Actual)Interventional2009-03-24Completed
Radical CUREfor MAlaria Among Highly Mobile and Hard-to-reach Populations in the Guyanese Shield [NCT05540470]5,000 participants (Anticipated)Interventional2022-09-12Not yet recruiting
Evaluation of Weekly Tafenoquine (SB 252263 / WR 238605) Compared to Placebo for Chemosuppression of Plasmodium Falciparum in Western Kenya [NCT02491606]Phase 2249 participants (Actual)Interventional1997-05-31Completed
A Five-cohort, Randomized, Open-label, Parallel-group Study to Evaluate the Pharmacokinetics of a Single Dose of Tafenoquine (SB252263) 300mg When Co-administered With the Artemisinin-based Combination Therapies (ACT) Artemether + Lumefantrine (AL) and Di [NCT02184637]Phase 1120 participants (Actual)Interventional2014-07-31Completed
A Randomized, Open-label, Single-period, Parallel-group Study in Healthy Subjects to Determine the Effects of Dissolution Profile on the Pharmacokinetics (Via Both Venous and Peripheral Micro-samples) of Single Oral 300 mg Doses of Tafenoquine (SB-252263) [NCT02751294]Phase 114 participants (Actual)Interventional2016-05-31Completed
A Phase 1, Multi-center, Single-masked, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Ophthalmologic Safety and Pharmacodynamics of 300mg Single Doses of Tafenoquine (SB 252263) in Adult Healthy Volunteers [NCT02658435]Phase 1486 participants (Actual)Interventional2016-02-02Completed
Single Low Dose Tafenoquine to Reduce P. Falciparum Transmission in Mali (NECTAR2) [NCT04609098]Phase 280 participants (Actual)Interventional2020-10-29Completed
Health Care Provider Use of Plasmodium Vivax Radical Cure (RC) With Tafenoquine or Primaquine After Semi-quantitative G6PD Testing: A Feasibility Study in Peru [NCT05361486]40 participants (Anticipated)Observational2023-08-28Recruiting
Does Artemisinin Combination Treatment Reduce the Radical Curative Efficacy of High Dose Tafenoquine for Plasmodium Vivax Malaria? [NCT05788094]Phase 4388 participants (Anticipated)Interventional2023-06-26Recruiting
A Randomized, Active-control, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults [NCT01290601]Phase 270 participants (Actual)Interventional2003-09-15Terminated(stopped due to Failure to meet pre-specified endpoint for the day 28 cure rate)
Study 200894: A Double-blind, Double-dummy, Randomized, Parallel Group, Placebo-controlled Superiority Study to Evaluate the Efficacy and Safety of Tafenoquine (SB-252263, WR238605) Co-administered With Dihydroartemisinin-piperaquine (DHA-PQP) for the Rad [NCT02802501]Phase 3150 participants (Actual)Interventional2018-04-08Completed
A Double-blind Placebo-controlled Study to Assess the Efficacy and Safety of Oral Tafenoquine Versus Placebo in Patients With Mild to Moderate COVID-19 Disease [NCT04533347]Phase 286 participants (Actual)Interventional2021-02-19Completed
Operational Feasibility of Appropriate Plasmodium Vivax Radical Cure With Tafenoquine or Primaquine After Quantitative G6PD Testing in Thailand [NCT05753150]187 participants (Actual)Observational2022-05-23Completed
An Open Label, Non-comparative, Multicenter Study to Assess the Pharmacokinetics, Safety and Efficacy of Tafenoquine (SB-252263, WR238605) in the Treatment of Pediatric Subjects With Plasmodium Vivax Malaria [NCT02563496]Phase 260 participants (Actual)Interventional2017-02-06Completed
Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients [NCT04411836]Phase 3960 participants (Anticipated)Interventional2021-04-25Recruiting
A Randomized, Double Blind, Placebo Controlled Evaluation of Weekly Tafenoquine (WR 238605/SB252263) Compared to Mefloquine for Chemosuppression of Plasmodium Falciparum in Western Kenya [NCT02488980]Phase 2306 participants (Actual)Interventional2000-05-31Completed
A Randomized, Placebo-Controlled Study to Evaluate the Effect of Tafenoquine (SB252263) on the Electrocardiogram (ECG) With Focus on Cardiac Repolarization (QTc Duration) in Healthy Subjects [NCT01928914]Phase 1260 participants (Actual)Interventional2011-07-26Completed
Breastfed Child Exposure to Tafenoquine and Primaquine During Treatment in Lactating Women: a Pharmacokinetic Study in Healthy Volunteers [NCT04984759]Phase 448 participants (Anticipated)Interventional2023-07-01Not yet recruiting
Operational Feasibility of Appropriate Radical Cure of Plasmodium Vivax With Tafenoquine or Primaquine After Quantitative G6PD Testing in Brazil [NCT05096702]16,000 participants (Actual)Observational2021-09-09Active, not recruiting
A Randomized, Double-blind, Placebo-controlled Evaluation of Increasing Doses of Weekly Tafenoquine for Chemosuppression of Plasmodium Falciparum in Semi-immune Adults Living in the Kassena-Nankana District of Northern Ghana [NCT02488902]Phase 2521 participants (Actual)Interventional1998-08-31Completed
A Randomized, Double-Blind, Double Dummy, Comparative, Multicenter Study to Assess the Incidence of Hemolysis, Safety, and Efficacy of Tafenoquine (SB-252263, WR238605) Versus Primaquine in the Treatment of Subjects With Plasmodium Vivax Malaria [NCT02216123]Phase 3251 participants (Actual)Interventional2015-04-30Completed
A Multi-centre, Double-blind, Randomised, Parallel-group, Active Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Tafenoquine (SB-252263, WR238605) in Subjects With Plasmodium Vivax Malaria. [NCT01376167]Phase 2851 participants (Actual)Interventional2014-04-24Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT01290601 (5) [back to overview]Fever Clearance Time (FCT)
NCT01290601 (5) [back to overview]Adequate Clinical Response (ACR) of Tafenoquine: 28 Day Cure Rate
NCT01290601 (5) [back to overview]Number of Subjects Without Relapse of P. Vivax
NCT01290601 (5) [back to overview]Parasite and Gametocyte Clearance Time (PCT and GCT)
NCT01290601 (5) [back to overview]Safety and Tolerability of Tafenoquine as Defined by Most Common Adverse Events (AEs)
NCT01376167 (31) [back to overview]Time Lost by Participants or Care Givers From Normal Occupation
NCT01376167 (31) [back to overview]Time Lost by Participants or Care Givers From Normal Occupation
NCT01376167 (31) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs) Potentially Related to Hemoglobin Decrease
NCT01376167 (31) [back to overview]Number of Participants With TEAEs by Maximum Intensity
NCT01376167 (31) [back to overview]Number of Participants With TEAEs and Serious TEAEs
NCT01376167 (31) [back to overview]Number of Participants With Retinal Changes From Baseline
NCT01376167 (31) [back to overview]Number of Participants With Retinal Changes From Baseline
NCT01376167 (31) [back to overview]Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range
NCT01376167 (31) [back to overview]Number of Participants With Keratopathy
NCT01376167 (31) [back to overview]Number of Participants With Keratopathy
NCT01376167 (31) [back to overview]Number of Participants With Hemoglobin Decline From Baseline Over First 29 Days
NCT01376167 (31) [back to overview]Number of Participants With Hematology Laboratory Data Outside the Reference Range
NCT01376167 (31) [back to overview]Number of Participants With Gastrointestinal Disorders
NCT01376167 (31) [back to overview]Number of Participants With Action Taken to Treat Recurrence Episode of P Vivax Malaria
NCT01376167 (31) [back to overview]Number of Participants With Action Taken to Treat Recurrence Episode of P Vivax Malaria
NCT01376167 (31) [back to overview]Incidence of Visual Field Abnormalities Based on Best Corrected Visual Acuity Test Scores
NCT01376167 (31) [back to overview]Incidence of Visual Field Abnormalities Based on Best Corrected Visual Acuity Test Scores
NCT01376167 (31) [back to overview]Cost Incurred With Purchase of Medications Associated With Recurrence Episode of Malaria
NCT01376167 (31) [back to overview]Cost Incurred With Purchase of Medications Associated With Recurrence Episode of Malaria
NCT01376167 (31) [back to overview]Cost Associated With Recurrence Episode of P Vivax Malaria
NCT01376167 (31) [back to overview]Cost Associated With Recurrence Episode of P Vivax Malaria
NCT01376167 (31) [back to overview]Change From Baseline in Percent Methemoglobin
NCT01376167 (31) [back to overview]Volume of Distribution (Vc/F) of TQ
NCT01376167 (31) [back to overview]Time to Recurrence of P Vivax Malaria
NCT01376167 (31) [back to overview]Time to Parasite Clearance
NCT01376167 (31) [back to overview]Time to Fever Clearance
NCT01376167 (31) [back to overview]Oral Clearance (CL/F) of TQ
NCT01376167 (31) [back to overview]Number of Participants With Recurrence-free Efficacy at 6 Months Post Dose
NCT01376167 (31) [back to overview]Number of Participants With Recurrence-free Efficacy at 4 Months Post Dose
NCT01376167 (31) [back to overview]Number of Participants With Acute Renal Failure
NCT01376167 (31) [back to overview]Number of Participants Who Received Blood Transfusion
NCT02216123 (34) [back to overview]Cost Associated With a Hemolysis Event
NCT02216123 (34) [back to overview]Cost Incurred With Purchase of Medications Associated With Hemolysis Event
NCT02216123 (34) [back to overview]Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to a Hemolysis Event
NCT02216123 (34) [back to overview]Number of Participants With Action Taken to Treat a Hemolysis Event
NCT02216123 (34) [back to overview]Number of Participants With P. Falciparum
NCT02216123 (34) [back to overview]Number of Participants With Recrudescence
NCT02216123 (34) [back to overview]Oral Clearance (CL/F) of TQ
NCT02216123 (34) [back to overview]Percentage of Participants With Clinically Relevant Hemolysis.
NCT02216123 (34) [back to overview]Rate of Relapse-free Efficacy at Four Months Post Dose
NCT02216123 (34) [back to overview]Rate of Relapse-free Efficacy at Six Months Post Dose
NCT02216123 (34) [back to overview]Time to Fever Clearance
NCT02216123 (34) [back to overview]Time to Gametocyte Clearance
NCT02216123 (34) [back to overview]Time to Parasite Clearance
NCT02216123 (34) [back to overview]Time to Relapse of P. Vivax Malaria
NCT02216123 (34) [back to overview]Volume of Distribution (Vc/F) of TQ
NCT02216123 (34) [back to overview]Change From Baseline in Percent Methemoglobin
NCT02216123 (34) [back to overview]Change From Baseline in Pulse Rate
NCT02216123 (34) [back to overview]Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP)
NCT02216123 (34) [back to overview]Change From Baseline in Temperature
NCT02216123 (34) [back to overview]Cost Associated With Relapse Episode of P Vivax Malaria
NCT02216123 (34) [back to overview]Cost Associated With Relapse Episode of P Vivax Malaria
NCT02216123 (34) [back to overview]Cost Incurred With Purchase of Medications Associated With Relapse Episode of P. Vivax Malaria
NCT02216123 (34) [back to overview]Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria
NCT02216123 (34) [back to overview]Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria
NCT02216123 (34) [back to overview]Number of Participants With Abnormal Urinalysis Dipstick Results
NCT02216123 (34) [back to overview]Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria
NCT02216123 (34) [back to overview]Number of Participants With Change in Best Corrected Visual Acuity Test Scores
NCT02216123 (34) [back to overview]Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range
NCT02216123 (34) [back to overview]Number of Participants With Electrocardiogram (ECG) Findings
NCT02216123 (34) [back to overview]Number of Participants With Genetically Homologous and Genetically Heterologous P. Vivax Infections
NCT02216123 (34) [back to overview]Number of Participants With Hematology Laboratory Data Outside the Reference Range
NCT02216123 (34) [back to overview]Number of Participants With Keratopathy
NCT02216123 (34) [back to overview]Number of Participants With Retinal Changes From Baseline
NCT02216123 (34) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
NCT02488980 (4) [back to overview]Time to a Single Positive Smear
NCT02488980 (4) [back to overview]Safety (SAEs and AEs)
NCT02488980 (4) [back to overview]Prophylactic Outcome Defined by the Subject Having no Positive Smears
NCT02488980 (4) [back to overview]Protective Efficacy Based on Two Consecutive Positive Smears
NCT02563496 (7) [back to overview]Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
NCT02563496 (7) [back to overview]Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
NCT02563496 (7) [back to overview]Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
NCT02563496 (7) [back to overview]Number of Participants With Hemoglobin Decline From Baseline Over First 10 Days
NCT02563496 (7) [back to overview]Number of Participants With Gastrointestinal Adverse Events
NCT02563496 (7) [back to overview]Number of Participants With Relapse-Free Efficacy at 4 Months
NCT02563496 (7) [back to overview]Area Under the Curve From Time 0 Extrapolated to Infinite Time (AUC[0-infinity]) of Tafenoquine by Weight Band in Participants Aged >=2 Years to <16 Years (Weighing >=5 kg)
NCT02802501 (20) [back to overview]Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT02802501 (20) [back to overview]Number of Participants With Worst Case Respiratory Rate Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT02802501 (20) [back to overview]Number of Participants With Worst Case Pulse Rate Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT02802501 (20) [back to overview]Number of Participants With Worst Case Body Temperature Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT02802501 (20) [back to overview]Number of Participants With Protocol-defined SAE (Hemoglobin Drop)
NCT02802501 (20) [back to overview]Number of Participants With Hematology Values Outside Clinical Concern Range
NCT02802501 (20) [back to overview]Number of Participants With Gastrointestinal AEs
NCT02802501 (20) [back to overview]Time to Parasite Clearance
NCT02802501 (20) [back to overview]Number of Participants With Chemistry Values Outside Clinical Concern Range
NCT02802501 (20) [back to overview]Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Double-blind Treatment Phase
NCT02802501 (20) [back to overview]Change From Baseline in QT Interval Corrected by Fridericia's Formula (QTcF)
NCT02802501 (20) [back to overview]Change From Baseline in Methemoglobin/ Total Hemoglobin
NCT02802501 (20) [back to overview]Time to Relapse of P. Vivax Malaria
NCT02802501 (20) [back to overview]Time to Fever Clearance
NCT02802501 (20) [back to overview]Percentage of Participants With Relapse-free Efficacy at Six Months After Administration of Tafenoquine With DHA-PQP and Primaquine+DHA-PQP
NCT02802501 (20) [back to overview]Percentage of Participants With Relapse-free Efficacy at Six Months After Administration of Tafenoquine With DHA-PQP and DHA-PQP Alone
NCT02802501 (20) [back to overview]Percentage of Participants With Relapse-free Efficacy at Six Months After Administration of Primaquine With DHA-PQP and DHA-PQP Alone
NCT02802501 (20) [back to overview]Percentage of Participants With Relapse-free Efficacy at Four Months After Administration of Tafenoquine With DHA-PQP and DHA-PQP Alone
NCT02802501 (20) [back to overview]Number of Participants With Recrudescence
NCT02802501 (20) [back to overview]Number of Participants With Electrocardiogram (ECG) Values Outside Clinical Concern Range-QT Interval Corrected Using Fredericia's Formula (QTcF)

Fever Clearance Time (FCT)

Measure of body temperature every 12 hours through day 7 was used to determine the time (to nearest 12 hours) from initiation of treatment until subjects temperature decreased to 37.2C and remained at or below that level for a minimum of 24 hours. (NCT01290601)
Timeframe: through day 7

InterventionHours (Mean)
Cohort 1 Tafenoquine41.5
Cohort 1-Chloroquine24.7

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Adequate Clinical Response (ACR) of Tafenoquine: 28 Day Cure Rate

A subject will be considered a success (cure) if they have an Adequate Clinical Response (ACR). Tafenoquine was efficacious if the lower bound of the two-sided 90% confidence interval for the day 28 cure rate was not less than 85% (NCT01290601)
Timeframe: 28 Days

,
InterventionParticipants (Count of Participants)
Adequate Clinical Response (ACR)Early Treatment FailureLate Treatment Failure
Cohort 1 Tafenoquine4051
Cohort 1-Chloroquine2202

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Number of Subjects Without Relapse of P. Vivax

"Number of subjects without relapse of P. vivax at 2, 3 and 4 months~- Blood smears were obtained at Days 28, 60, 90 and 120 to confirm the continued absence of P. vivax parasitemia" (NCT01290601)
Timeframe: Day 28, Months 2, 3 and 4

,
Interventionparticipants (Number)
Cleared at Day 28Relapsed by Day 60Relapsed by Day 90Relapsed by Day 120Without Relapse by Day 120Unevaluable by Day 120
Cohort 1 Tafenoquine40000355
Cohort 1-Chloroquine22011192

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Parasite and Gametocyte Clearance Time (PCT and GCT)

Serial blood smears to detect the presence of P. vivax parasites and gametocytes, conducted every 12 hours up to and including day 7, until blood smear became negative were utilized to determine the time to clearance. PCT and GCT were considered cleared if 2 consecutive blood smears were negative. (NCT01290601)
Timeframe: up to day 7 after baseline smear

,
InterventionHours (Mean)
Parasite Clearance TimeGametocyte Clearance Time
Cohort 1 Tafenoquine83.448.3
Cohort 1-Chloroquine40.022.7

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Safety and Tolerability of Tafenoquine as Defined by Most Common Adverse Events (AEs)

To evaluate the safety and tolerability of the tafenoquine dosing regimens as defined by the most common AE's overall, occurring in >10% of subjects in either treatment group (NCT01290601)
Timeframe: 90 Days

,
InterventionAEs (Number)
Blood methemoglobin presentHeadacheKeratopathyUpper respiratory tract infectionDizzinessRetinopathyEosinophiliaAbdominal painNauseaThrombocytopeniaEosinophil count increasedPyrexia
Cohort 1 Tafenoquine46141413129866655
Cohort 1-Chloroquine2240531753033

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Time Lost by Participants or Care Givers From Normal Occupation

Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The reported time lost due to recurrence episode of P vivax malaria has been summarized by category and by site. Where categories by site have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionDays (Number)
Brazil, HouseworkBrazil, FarmingBrazil, paid employmentBrazil, OtherCambodia, FarmingEthiopia, HouseworkEthiopia, FarmingEthiopia, StudentEthiopia, Paid employmentEthiopia, OtherPeru, HouseworkPeru, FarmingPeru, StudentPeru, Paid employmentPeru, OtherPhilippines, FarmingThailand, paid employmentThailand, Other
First Malaria Recurrence18831742.5321241916260201

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Time Lost by Participants or Care Givers From Normal Occupation

Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The reported time lost due to recurrence episode of P vivax malaria has been summarized by category and by site. Where categories by site have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionDays (Number)
Brazil, HouseworkBrazil, FarmingBrazil, paid employmentBrazil, OtherCambodia, FarmingEthiopia, HouseworkEthiopia, FarmingEthiopia, StudentEthiopia, Paid employmentEthiopia, OtherPeru, HouseworkPeru, FarmingPeru, StudentPeru, Paid employmentPeru, OtherThailand, paid employmentThailand, Other
First Malaria Recurrence Follow-up00052433047292868.53200

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Number of Participants With TEAEs by Maximum Intensity

An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is defined as AEs with an onset date and time on or after that of the start of first dose of study medication (including CQ). Number of participants with AEs based on severity has been presented. (NCT01376167)
Timeframe: Up to Day 180

,,
InterventionParticipants (Number)
Mild or Grade 1Moderate or Grade 2Severe or Grade 3Grade 4Grade 5
CQ Only3052310
PQ + CQ3837100
TQ + CQ7089201

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Number of Participants With TEAEs and Serious TEAEs

An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations and is associated with possible drug induced liver injury with hyperbilirubinemia. TEAEs is defined as AEs with an onset date and time on or after that of the start of first dose of study medication (including CQ). Number of participants with TEAEs and serious TEAEs have been presented. (NCT01376167)
Timeframe: Up to Day 180

,,
InterventionParticipants (Number)
TEAEsSerious TEAEs
CQ Only866
PQ + CQ764
TQ + CQ16421

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Number of Participants With Retinal Changes From Baseline

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment. The number of participants with definite retinal change and questionable (ques) retinal change from Baseline was presented. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Baseline and up to Day 180

InterventionParticipants (Number)
Day 29, Definite change, right eyeDay 29, Ques change, right eyeDay 29, Definite change, left eyeDay 29, Ques change, left eyeDay 90, Definite change, right eyeDay 90, Ques change, right eyeDay 90, Definite change, left eyeDay 90, Ques change, left eye
PQ + CQ00001102

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Number of Participants With Retinal Changes From Baseline

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment. The number of participants with definite retinal change and questionable (ques) retinal change from Baseline was presented. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Baseline and up to Day 180

,
InterventionParticipants (Number)
Day 29, Definite change, right eyeDay 29, Ques change, right eyeDay 29, Definite change, left eyeDay 29, Ques change, left eyeDay 90, Definite change, right eyeDay 90, Ques change, right eyeDay 90, Definite change, left eyeDay 90, Ques change, left eyeDay 180, Definite change, right eyeDay 180, Ques change, right eyeDay 180, Definite change, left eyeDay 180, Ques change, left eye
CQ Only101010100000
TQ + CQ000010110000

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Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range

Blood samples were collected for the evaluation of clinical chemistry parameters including Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos), Aspartate Aminotransferase (AST), bilirubin, creatine kinase, creatinine, glomerular filtration rate (GFR), indirect bilirubin and urea. The number of participants with clinical chemistry laboratory data outside the extended normal range (F3) was presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 120

,,
InterventionParticipants (Number)
ALT, HighAlk Phos, HighAST, HighBilirubin, HighCreatine kinase, HighCreatinine, HighGFR, LowIndirect bilirubinUrea, High
CQ Only1135188001142
PQ + CQ51212800846
TQ + CQ1017235112285

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Number of Participants With Keratopathy

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. The number of participants displaying keratopathy in each eye was summarized for each visit. The number of participants with new keratopathy at any time post Baseline was also reported. Ophthalmic Safety Population comprised of all participants in the Safety Population who have results from any eye assessments. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

,
InterventionParticipants (Number)
Baseline; right eyeBaseline; left eyeDay 1; right eyeDay 1; left eyeDay 29; right eyeDay 29; left eyeDay 90; right eyeDay 90; left eyeDay 180; right eyeDay 180; left eyeAny time post Baseline; right eyeAny time post Baseline; left eye
PQ + CQ000000000000
TQ + CQ000000100010

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Number of Participants With Keratopathy

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. The number of participants displaying keratopathy in each eye was summarized for each visit. The number of participants with new keratopathy at any time post Baseline was also reported. Ophthalmic Safety Population comprised of all participants in the Safety Population who have results from any eye assessments. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Baseline; right eyeBaseline; left eyeDay 1; right eyeDay 1; left eyeDay 29; right eyeDay 29; left eyeDay 90; right eyeDay 90; left eyeAny time post Baseline; right eyeAny time post Baseline; left eye
CQ Only0000000000

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Number of Participants With Hemoglobin Decline From Baseline Over First 29 Days

Glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency is known to be a risk factor for hemolysis in participants treated with 8-aminoquinolines. Blood samples were collected for the evaluation of hemoglobin levels. Hemoglobin decreases of >=30% or >3 grams/deciliter (g/dL) from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL in the first 15 days of the study were considered as protocol defined serious adverse events (SAEs). Number of participants with maximum hemoglobin decline from Baseline over first 29 days of study has been summarized. Safety Population consisted of all randomized participants who received at least one dose of study medication. (NCT01376167)
Timeframe: Baseline and up to Day 29

,,
InterventionParticipants (Number)
<=20 grams/liter (g/L)>20g/L to <=30 g/L>30 g/L or >=30%
CQ Only120112
PQ + CQ114123
TQ + CQ2143114

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Number of Participants With Hematology Laboratory Data Outside the Reference Range

Blood samples were collected for the evaluation of hematology parameters including eosinophils, leukocytes, lymphocytes, neutrophils, platelets, reticulocytes and methemoglobin. The number of participants with hematology laboratory data outside the extended normal range (F3) was presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 120

,,
InterventionParticipants (Number)
Blood eosinophils, HighBlood leukocytes, LowBlood lymphocytes, LowBlood lymphocytes, HighBlood neutrophils, LowBlood platelets, LowBlood reticulocytes, HighMethemoglobin, High
CQ Only180723214724
PQ + CQ2820137158511
TQ + CQ3834325351415

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Number of Participants With Gastrointestinal Disorders

Gastrointestinal tolerability was analyzed by the number of par experiencing gastrointestinal disorders such as abdominal pain, heartburn, diarrhea, constipation, nausea, and vomiting. The number of participants with gastrointestinal disorders for each treatment group has been summarized. (NCT01376167)
Timeframe: Up to Day 180

,,
InterventionParticipants (Number)
NauseaVomitingAbdominal pain upperDiarrhoeaAbdominal painDyspepsia
CQ Only12913655
PQ + CQ9117562
TQ + CQ2122111586

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Number of Participants With Action Taken to Treat Recurrence Episode of P Vivax Malaria

Health outcomes were evaluated based on the actions taken by the participants to treat recurrence episode of P vivax malaria. The reported action taken by site is summarized. Where no action by site have been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Brazil, NothingBrazil, Drug shopBrazil, Trial clinicBrazil, OtherCambodia, NothingEthiopia, NothingEthiopia, Another clinicEthiopia, OtherEthiopia, Trial clinicPeru, NothingPeru, Drug shopPeru, Trial clinicPeru, Another clinicPeru, OtherPhilippines, NothingThailand, NothingThailand, Drug shopThailand, Trial clinicThailand, In hospital
First Malaria Recurrence212622131211018611015111131

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Number of Participants With Action Taken to Treat Recurrence Episode of P Vivax Malaria

Health outcomes were evaluated based on the actions taken by the participants to treat recurrence episode of P vivax malaria. The reported action taken by site is summarized. Where no action by site have been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Brazil, NothingBrazil, Drug shopBrazil, Trial clinicBrazil, OtherCambodia, NothingEthiopia, NothingEthiopia, Another clinicEthiopia, OtherEthiopia, Trial clinicPeru, NothingPeru, Drug shopPeru, Trial clinicPeru, Another clinicPeru, OtherThailand, NothingThailand, Drug shopThailand, Trial clinicThailand, In hospital
First Malaria Recurrence Follow-up507601413001006354116000

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Incidence of Visual Field Abnormalities Based on Best Corrected Visual Acuity Test Scores

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Best corrected visual acuity was assessed individually for each eye. Scores were recorded as a ratio. The values were used to derive a logMAR score for statistical analysis where logMAR=-1x log10 (ratio score). The mean and standard deviation of logMAR score for each treatment group has been summarized. High scores were associated with worse vision, and low scores with better vision. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

,
InterventionlogMAR scores (Mean)
Baseline; right eyeBaseline; left eyeDay 29; right eyeDay 29; left eyeDay 90; right eyeDay 90; left eyeDay 180; right eyeDay 180; left eye
PQ + CQ0.0290.0480.0210.0450.0160.0410.0000.000
TQ + CQ0.0460.0390.0490.0320.0380.0280.0330.033

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Incidence of Visual Field Abnormalities Based on Best Corrected Visual Acuity Test Scores

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Best corrected visual acuity was assessed individually for each eye. Scores were recorded as a ratio. The values were used to derive a logMAR score for statistical analysis where logMAR=-1x log10 (ratio score). The mean and standard deviation of logMAR score for each treatment group has been summarized. High scores were associated with worse vision, and low scores with better vision. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionlogMAR scores (Mean)
Baseline; right eyeBaseline; left eyeDay 29; right eyeDay 29; left eyeDay 90; right eyeDay 90; left eye
CQ Only0.0410.0480.0390.0320.0440.041

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Cost Incurred With Purchase of Medications Associated With Recurrence Episode of Malaria

"Health outcomes were evaluated based on the cost of medications purchased. The reported total medication cost for paracetamol associated with recurrence episode of P vivax malaria has been reported by site. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Medications recorded as Other and medications without costs are excluded from the analysis. Only those participants with data available at the specified data points were analyzed." (NCT01376167)
Timeframe: Up to Day 180

InterventionUSD (Mean)
Peru, n=23, 3Brazil, n=6, 0
First Malaria Recurrence0.491.70

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Cost Incurred With Purchase of Medications Associated With Recurrence Episode of Malaria

"Health outcomes were evaluated based on the cost of medications purchased. The reported total medication cost for paracetamol associated with recurrence episode of P vivax malaria has been reported by site. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Medications recorded as Other and medications without costs are excluded from the analysis. Only those participants with data available at the specified data points were analyzed." (NCT01376167)
Timeframe: Up to Day 180

InterventionUSD (Mean)
Peru, n=23, 3
First Malaria Recurrence Follow-up0.32

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Cost Associated With Recurrence Episode of P Vivax Malaria

Health outcomes were evaluated based on the total costs spent on treatment, transport, medication and tests. The cost was summarized according to the place at which the participant went to for care (drug shop, trial clinic, other clinic, hospital (inpatient/outpatient), traditional healer, other). The reported costs by type and by site has been summarized. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionUS Dollars (USD) (Mean)
Brazil (Enrollment clinic for care)Peru (Enrollment clinic for care)Peru (Attended another clinic)Peru (Other location for care)
First Malaria Recurrence Follow-up6.158.543.941.30

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Cost Associated With Recurrence Episode of P Vivax Malaria

Health outcomes were evaluated based on the total costs spent on treatment, transport, medication and tests. The cost was summarized according to the place at which the participant went to for care (drug shop, trial clinic, other clinic, hospital (inpatient/outpatient), traditional healer, other). The reported costs by type and by site has been summarized. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Up to Day 180

InterventionUS Dollars (USD) (Mean)
Brazil (Drug shop for care)Brazil (Enrollment clinic for care)Brazil (other location for care)Peru (Drug shop for care)Peru (Enrollment clinic for care)Peru (Attended another clinic)Peru (Other location for care)Thailand (Drug shop for care)Thailand (Enrollment clinic for care)Thailand (In-hospital care)
First Malaria Recurrence4.766.174.231.478.782.710.724.6019.156.13

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Change From Baseline in Percent Methemoglobin

Methemoglobin assessment was made with the aid of a non-invasive signal extraction pulse CO-Oximeter handheld machine (Masimo). The change from Baseline in percent methemoglobin by treatment, time and sex has been summarized. The last assessment performed prior to the first dose of study medication (CQ or randomized treatment) was considered as Baseline. Change from Baseline was calculated as the post baseline assessment minus the Baseline assessment for percent methemoglobin. Only those participants with data available at the specified data points were analyzed. (NCT01376167)
Timeframe: Baseline and up to Day 120

,,
InterventionPercent Methemoglobin (Mean)
Day 2, MaleDay 2, FemaleDay 3, MaleDay 3, FemaleDay 5, MaleDay 5, FemaleDay 8, MaleDay 8, FemaleDay 11, MaleDay 11, FemaleDay 15, MaleDay 15, FemaleDay 22, MaleDay 22, FemaleDay 29, MaleDay 29, FemaleDay 60, MaleDay 60, FemaleDay 120, MaleDay 120, Female
CQ Only-0.18-0.22-0.15-0.20-0.28-0.20-0.12-0.16-0.07-0.130.12-0.080.07-0.05-0.10-0.180.440.190.200.10
PQ + CQ-0.10-0.01-0.020.111.280.903.012.583.613.413.513.631.961.860.580.490.200.160.370.37
TQ + CQ-0.030.10-0.010.260.421.370.982.041.172.130.941.670.540.930.230.24-0.100.030.07-0.03

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Volume of Distribution (Vc/F) of TQ

Apparent population central volume of distribution of TQ (NCT01376167)
Timeframe: Day 2, Day 8, Day 15, Day 29 and Day 60

InterventionLiters (Median)
Participants in TQ Only Arms915

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Time to Recurrence of P Vivax Malaria

Recurrence was defined as the first confirmed presence of P vivax asexual stage parasites after clearance of initial parasitemia following CQ treatment. Time to recurrence was defined as the time (in days) from initial parasite clearance to recurrence. The time to recurrence was analyzed by the Kaplan-Meier method. NA indicates data was not available due to insufficient number of participants with events during the follow up period in the study. The median number of days to recurrence along with 95% confidence interval has been presented for each treatment group. (NCT01376167)
Timeframe: Up to Day 180

InterventionDays (Median)
CQ Only86
TQ + CQNA
PQ + CQNA

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Time to Parasite Clearance

Parasite clearance time was defined as time needed to clear asexual parasite from the blood that is, parasite numbers falling below the limit of detection in the thick blood smear and remaining undetectable after 6 to 12 hours. The time taken to achieve parasite clearance was analyzed using Kaplan Meier Methodology. The median parasite clearance time along with 95% confidence interval has been presented for each treatment group. (NCT01376167)
Timeframe: Up to Day 180

InterventionHours (Median)
CQ Only43
TQ + CQ45
PQ + CQ42

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Time to Fever Clearance

Fever clearance time was defined as time from first dose of treatment to the time when body temperature falls to normal within Study Days 1-4 and remains normal for at least 48 hours up to the Day 8 visit. Fever clearance was considered to have been achieved once an initial temperature of more than 37.40 degree Celsius is reduced to a value less than or equal to 37.40 degree Celsius and in the absence of value more than 37.40 degree Celsius in the following 48 hours up to the Day 8 visit. The time taken to achieve fever clearance was analyzed using Kaplan Meier Methodology. The median fever clearance time along with 95% confidence interval has been presented for each treatment group. (NCT01376167)
Timeframe: Up to Day 180

InterventionHours (Median)
CQ Only7
TQ + CQ7
PQ + CQ8

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Oral Clearance (CL/F) of TQ

Apparent population oral clearance of TQ (NCT01376167)
Timeframe: Day 2, Day 8, Day 15, Day 29 and Day 60

InterventionLiters per hour (Median)
Participants in TQ Only Arms2.96

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Number of Participants With Recurrence-free Efficacy at 6 Months Post Dose

A participant was considered to have demonstrated recurrence-free efficacy at 6 months if: a) Participant had non-zero P vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P vivax parasitemia defined as two negative asexual P vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval. c) Participant had no positive asexual P vivax parasite count at any assessment prior to or on Study Day 201 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 6 months. Participants were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites, or did not have a 6 month assessment. The number of participants with recurrence-free efficacy at 6 months has been summarized. (NCT01376167)
Timeframe: 6 months post dose

InterventionParticipants (Number)
CQ Only35
TQ + CQ155
PQ + CQ83

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Number of Participants With Recurrence-free Efficacy at 4 Months Post Dose

A participant (par) was considered to have demonstrated recurrence-free efficacy at 4 months if: a) Par had non-zero P vivax asexual parasite count at Baseline. b) Par showed initial clearance of P vivax parasitemia. c) Par had no positive asexual P vivax parasite count at any assessment prior to or on Study Day 130 following initial parasite clearance. d) Par did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment after Study Day 109 (up to and including Study Day 130). e) Par is parasite-free at 4 months defined as a negative asexual P vivax parasite count at the first parasite assessment performed after Study Day 109 (up to and including Study Day 130). Par were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites or did not have a 4 month assessment. The number of par with recurrence-free efficacy at 4 months has been summarized. (NCT01376167)
Timeframe: 4 months post dose

InterventionParticipants (Number)
CQ Only47
TQ + CQ177
PQ + CQ90

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Number of Participants With Acute Renal Failure

There were no participants with acute renal failure in the study. (NCT01376167)
Timeframe: Up to Day 180

InterventionParticipants (Number)
CQ Only0
TQ + CQ0
PQ + CQ0

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Number of Participants Who Received Blood Transfusion

The number of participants who received blood transfusion as a result of hemoglobin decline has been summarized. (NCT01376167)
Timeframe: Up to Day 180

InterventionParticipants (Number)
CQ Only0
TQ + CQ0
PQ + CQ0

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Cost Associated With a Hemolysis Event

Health outcomes were evaluated based on cost incurred due to clinically relevant hemolysis. The total cost was evaluated based on the amount spent on treatment, transport, medication and test. The costs associated with hemolysis event has been presented. The aim of this outcome measure was to determine the cost to a participant due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major cost differences with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan. (NCT02216123)
Timeframe: Up to Day 180

InterventionUSD (Mean)
Participants With Clinically Relevant Hemolysis9.174

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Cost Incurred With Purchase of Medications Associated With Hemolysis Event

"Health outcomes were evaluated based on the cost of medications purchased. The total medication cost associated with hemolysis event has been presented. Medications recorded as Other and medications without costs are excluded from the analysis. The aim of this outcome measure was to determine the cost to a participant due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major cost differences with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan." (NCT02216123)
Timeframe: Up to Day 180

InterventionUSD (Mean)
Participants With Clinically Relevant Hemolysis0

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Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to a Hemolysis Event

Health outcomes were evaluated based on total time lost by participants or care givers due to a hemolysis event. The number of participants or care givers who took days off from work due to a hemolysis event has been presented based on the normal occupation. The aim of this outcome measure was to determine the time taken off by participants due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major differences in time taken off by participants with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan. (NCT02216123)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Participants With Clinically Relevant Hemolysis0

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Number of Participants With Action Taken to Treat a Hemolysis Event

Health outcomes were evaluated based on the actions taken by the participants to treat hemolysis events. The number of participants in Brazil who attended the trial clinic to treat a hemolysis event has been presented. The aim of this outcome measure was to determine the action taken by a participant due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major differences in action taken by the participants with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan. (NCT02216123)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Participants With Clinically Relevant Hemolysis1

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Number of Participants With P. Falciparum

Microscopic blood slides (two thick film and one thin film slide) were prepared and examined for asexual parasite count. The number of participants with positive P. falciparum asexual parasite count post Baseline has been summarized for each treatment arm. (NCT02216123)
Timeframe: Up to Day 180

InterventionParticipants (Number)
TQ+CQ4
PQ+CQ3

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Number of Participants With Recrudescence

Recrudescence is defined as any P. vivax parasitemia occurring on or before Day 32 (that is, blood stage treatment failure). A participant was considered to have had a recrudescence if both of the following were true: a) Participant had a positive P. vivax asexual parasite count at Baseline and demonstrated clearance (that is, did not have two negative asexual P. vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval). b) Participant had a positive genetically homologous asexual P. vivax parasite count, after their zero count in Days 1 to 5, but on or before Study Day 32. The number of participants with recrudescence before Study Day 33 has been presented. (NCT02216123)
Timeframe: Up to Day 32

InterventionParticipants (Number)
TQ+CQ0
PQ+CQ0

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Oral Clearance (CL/F) of TQ

Apparent population oral clearance of TQ (NCT02216123)
Timeframe: Day 2, Day 3, Day 8, Day 15, Day 29, Day 60 and Day 180

InterventionLiters per hour (Median)
Participants in TQ Only Arms2.96

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Percentage of Participants With Clinically Relevant Hemolysis.

Clinically relevant hemolysis is defined as a decrease in hemoglobin of >=30% or >3 grams per deciliter (g/dL) from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL at any visit after the first dose of study medication. The percentage of participants with clinically relevant hemolysis has been summarized. Safety Population comprised of all randomized participants who received at least one dose of blinded study medication. (NCT02216123)
Timeframe: Up to Day 180

InterventionPercentage of participants (Number)
TQ+CQ2.41
PQ+CQ1.18

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Rate of Relapse-free Efficacy at Four Months Post Dose

A participant was considered to have demonstrated recurrence-free efficacy at 4 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P. vivax parasitemia. c) Participant had no positive asexual P. vivax parasite count at any assessment prior to or on Study Day 130 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment after Study Day 109 (up to and including Study Day 130). e) Participant is parasite-free at 4 months. The rate of relapse-free efficacy was estimated by Kaplan-Meier methodology. The percentage of participants who were relapse-free at 4 months post dose has been presented along with 95% confidence interval. (NCT02216123)
Timeframe: 4 months post dose

InterventionPercentage of participants (Number)
TQ+CQ82.3
PQ+CQ79.7

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Rate of Relapse-free Efficacy at Six Months Post Dose

A participant was considered to have demonstrated relapse-free efficacy at 6 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P. vivax parasitemia defined as two negative asexual P. vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval. c) Participant had no positive asexual P. vivax parasite count at any assessment prior to or on Study Day 201 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 6 months. The rate of relapse-free efficacy was estimated by Kaplan-Meier methodology. The percentage of participants who were relapse-free at 6 months post dose has been presented along with 95% confidence interval. (NCT02216123)
Timeframe: 6 months post dose

InterventionPercentage of participants (Number)
TQ+CQ72.7
PQ+CQ75.1

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Time to Fever Clearance

Fever clearance time is defined as the time from first dose of treatment to the time when body temperature falls to normal within Study Days 1-4 and remains normal for at least 48 hours up to the Day 8 visit. Fever clearance was considered to have been achieved once an initial temperature of more than 37.4 degree Celsius is reduced to a value less than or equal to 37.4 degree Celsius, in the absence of value more than 37.4 degree Celsius in the following 48 hours up to the Day 8 visit. The time taken to achieve fever clearance was analyzed by Kaplan-Meier method. (NCT02216123)
Timeframe: Up to Day 9

InterventionHours (Median)
TQ+CQ10
PQ+CQ13

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Time to Gametocyte Clearance

Gametocyte clearance time is defined as time from first dose until the first slide that was gametocyte negative and remained so at the next slide reading. The time taken to achieve gametocyte clearance was analyzed by Kaplan-Meier method. (NCT02216123)
Timeframe: Up to Day 180

InterventionHours (Median)
TQ+CQ38
PQ+CQ41

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Time to Parasite Clearance

Parasite clearance time is defined as time needed to clear asexual parasite from the blood that is, parasite numbers falling below the limit of detection in the thick blood smear and remaining undetectable after 6 to 12 hours later. The time to achieve parasite clearance was analyzed by Kaplan-Meier methodology. The median parasite clearance time along with 95% confidence interval has been presented for each treatment group. (NCT02216123)
Timeframe: Up to Day 180

InterventionHours (Median)
TQ+CQ41
PQ+CQ44

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Time to Relapse of P. Vivax Malaria

Relapse is defined by a positive blood smear with or without vivax symptoms. Relapse is described as any recurrence of malaria that occurred after Day 32 of the study. The time to relapse was analyzed by the Kaplan-Meier method. The median number of days to relapse along with 95% confidence interval has been presented for each treatment group. (NCT02216123)
Timeframe: Up to Day 180

InterventionDays (Median)
TQ+CQNA
PQ+CQNA

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Volume of Distribution (Vc/F) of TQ

Apparent population central volume of distribution of TQ (NCT02216123)
Timeframe: Day 2, Day 3, Day 8, Day 15, Day 29, Day 60 and Day 180

InterventionLiters (Median)
Participants in TQ Only Arms915

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Change From Baseline in Percent Methemoglobin

Methemoglbin is an oxidized and inactive form of hemoglobin. Methemoglobin assessment was made with the aid of a non-invasive signal extraction pulse CO-Oximeter handheld machine. The change from Baseline in percent methemoglobin by treatment, time and sex has been summarized. The latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo) was considered as Baseline value. Change from Baseline is the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Baseline and up to Day 120

,
InterventionPercent change (Mean)
Day 2, Male, n=114, 53Day 2, Female, n=52, 32Day 3, Male, n=114, 53Day 3, Female, n=52, 32Day 5, Male, n=113, 53Day 5, Female, n=52, 32Day 8, Male, n=112, 52Day 8, Female, n=52, 32Day 11, Male, n=112, 52Day 11, Female, n=51, 32Day 15, Male, n=113, 52Day 15, Female, n=52, 32Day 22, Male, n=112, 52Day 22, Female, n=52, 32Day 29, Male, n=111, 52Day 29, Female, n=52, 32Day 60, Male, n=107, 51Day 60, Female, n=52, 32Day 120, Male, n=109, 50Day 120, Female, n=50, 31
PQ+CQ0.02-0.060.030.170.891.322.632.813.303.443.263.611.582.300.460.840.200.14-0.010.04
TQ+CQ0.02-0.160.180.080.770.631.221.001.161.041.010.810.610.320.24-0.020.05-0.090.060.14

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Change From Baseline in Pulse Rate

Vital signs were measured twice a day on Days 1 through 3, at least 4 hours apart, and immediately prior to PK measurements. The mean and standard deviation of pulse rate has been presented. The values presented does not include Day 3 assessments for participant number 570. Baseline value is defined as the latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo). Change from Baseline is the value at post dose minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Baseline and up to Day 180

,
Interventionbeats per minute (Mean)
Day 1 assessment 4; n=161, 84Day 2 assessment 1; n=166, 85Day 2 assessment 4; n=166, 85Day 3 assessment 1; n=166, 83Day 3 assessment 4; n=166, 82Day 8; n=164, 84Day 11; n=163, 84Day15; n=165, 84Day 22; n=164, 84Day 29; n=163, 84Day 60; n=160, 83Day 90; n=160, 82Day 120; n=159, 81Day 150; n=161, 82Day180; n=160, 83
PQ+CQ-9.3-9.9-11.8-18.2-17.5-14.6-15.5-16.9-16.8-17.5-18.5-18.6-19.1-17.9-18.3
TQ+CQ-10.8-9.9-11.9-15.1-16.5-12.7-13.4-13.5-14.7-16.9-16.7-16.3-16.7-16.8-18.0

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Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP)

Vital signs were measured twice a day on Days 1 through 3, at least 4 hours apart, and immediately prior to pharmacokinetic (PK) measurements. MAP was calculated as the sum of SBP and two times DBP divided by 3. The mean and standard deviation of SBP, DBP and MAP has been presented. The values presented does not include Day 3 assessments for participant number 570. Baseline value is defined as the latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo). Change from Baseline is the value at post dose minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Baseline and up to Day 180

,
Interventionmillimeter of mercury (mmHg) (Mean)
SBP, Day 1 assessment 4; n=161, 84SBP, Day 2 assessment 1; n=166, 85SBP, Day 2 assessment 4; n=166, 85SBP, Day 3 assessment 1; n=166, 83SBP, Day 3 assessment 4; n=166, 82SBP, Day 8; n=164, 84SBP, Day 11; n=163, 84SBP, Day15; n=165, 84SBP, Day 22; n=164, 84SBP, Day 29; n=163, 84SBP, Day 60; n=160, 83SBP, Day 90; n=160, 82SBP, Day 120; n=159, 81SBP, Day 150; n=161, 82SBP, Day180; n=160, 83DBP, Day 1 assessment 4; n=161, 84DBP, Day 2 assessment 1; n=166, 85DBP, Day 2 assessment 4; n=166, 85DBP, Day 3 assessment 1; n=166, 83DBP, Day 3 assessment 4; n=166, 82DBP, Day 8; n=164, 84DBP, Day 11; n=163, 84DBP, Day15; n=165, 84DBP, Day 22; n=164, 84DBP, Day 29; n=163, 84DBP, Day 60; n=160, 83DBP, Day 90; n=160, 82DBP, Day 120; n=159, 81DBP, Day 150; n=161, 82DBP, Day180; n=160, 83MAP, Day 1 assessment 4; n=161, 84MAP, Day 2 assessment 1; n=166, 85MAP, Day 2 assessment 4; n=166, 85MAP, Day 3 assessment 1; n=166, 83MAP, Day 3 assessment 4; n=166, 82MAP, Day 8; n=164, 84MAP, Day 11; n=163, 84MAP, Day15; n=165, 84MAP, Day 22; n=164, 84MAP, Day 29; n=163, 84MAP, Day 60; n=160, 83MAP, Day 90; n=160, 82MAP, Day 120; n=159, 81MAP, Day 150; n=161, 82MAP, Day180; n=160, 83
PQ+CQ-0.9-2.3-2.7-2.1-2.20.81.22.52.94.44.35.33.14.95.7-1.5-2.2-2.6-1.3-1.91.1-0.50.41.31.51.93.52.44.13.7-1.3-2.2-2.6-1.6-2.01.00.11.11.82.42.74.12.64.44.4
TQ+CQ1.20.4-0.8-0.6-2.72.21.33.23.32.64.43.83.84.43.71.1-0.1-0.8-0.2-1.90.9-0.01.51.20.93.12.73.33.22.91.10.0-0.8-0.3-2.21.30.42.01.91.53.53.13.53.63.2

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Change From Baseline in Temperature

Vital signs were performed twice a day on Days 1 through 3, at least 4 hours apart, and immediately prior to PK measurements. The mean and standard deviation of pulse rate has been presented. The values presented does not include Day 3 assessments for participant number 570. Baseline value is defined as the latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo). Change from Baseline is the value at post dose minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Baseline and up to Day 180

,
InterventionCelsius (Mean)
Day 1 assessment 4; n=161, 84Day 2 assessment 1; n=166, 85Day 2 assessment 4; n=166, 85Day 3 assessment 1; n=166, 83Day 3 assessment 4; n=166, 82Day 8; n=164, 84Day 11; n=163, 84Day15; n=165, 84Day 22; n=164, 84Day 29; n=163, 84Day 60; n=160, 83Day 90; n=160, 82Day 120; n=159, 81Day 150; n=161, 82Day180; n=160, 83
PQ+CQ-0.5-0.6-0.6-0.9-1.0-0.9-0.9-1.0-1.0-1.0-1.0-1.0-0.9-1.0-1.0
TQ+CQ-0.6-0.6-0.6-1.0-1.0-1.0-1.0-0.9-1.0-1.0-1.0-1.0-1.0-1.0-1.0

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Cost Associated With Relapse Episode of P Vivax Malaria

Health outcomes were evaluated based on the total costs spent on treatment, transport, medication and tests. The cost was summarized according to the place at which the participant went to for care (drug shop, trial clinic, other clinic, hospital emergency center, other). The costs associated with a relapse episode of P. vivax malaria has been presented. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 180

InterventionUS Dollars (USD) (Mean)
Brazil; enrollment clinic for care; n=19, 17Colombia; hospital emergency center; n=1,1Peru; enrollment clinic for care; n=32, 33Peru; attended another clinic; n=8, 30Thailand; enrollment clinic for care; n=0, 1Vietnam; drug shop for care;n=1, 2Vietnam; attended another clinic; n=0, 1
First Malaria Relapse Follow-up8.03216.7758.8153.9591.5342.8090.936

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Cost Associated With Relapse Episode of P Vivax Malaria

Health outcomes were evaluated based on the total costs spent on treatment, transport, medication and tests. The cost was summarized according to the place at which the participant went to for care (drug shop, trial clinic, other clinic, hospital emergency center, other). The costs associated with a relapse episode of P. vivax malaria has been presented. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 180

InterventionUS Dollars (USD) (Mean)
Brazil; enrollment clinic for care; n=19, 17Colombia; enrollment clinic for care; n=1,0Colombia; attended another clinic; n=1,0Colombia; hospital emergency center; n=1,1Peru; enrollment clinic for care; n=32, 33Peru; attended another clinic; n=8, 30Peru; Other; n=8, 0Vietnam; drug shop for care;n=1, 2Vietnam; Other; n=1, 0
First Malaria Relapse8.20842.7764.19416.7759.2441.6770.8180.7021.873

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Cost Incurred With Purchase of Medications Associated With Relapse Episode of P. Vivax Malaria

"Health outcomes were evaluated based on the cost of medications purchased. The total medication cost for paracetamol associated with relapse episode of P vivax malaria has been presented. Medications recorded as Other and medications without costs are excluded from the analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title)." (NCT02216123)
Timeframe: Up to Day 180

,
InterventionUSD (Mean)
Colombia; n=2, 1Peru; n=6, 2Vietnam; n=1, 1
First Malaria Relapse2.5160.4910.468
First Malaria Relapse Follow-up4.1940.3272.341

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Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria

Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The number of participants or care givers who had taken off from their normal occupation due to relapse episode of P vivax malaria has been presented by country. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Brazil; Housework; n=2, 1Brazil; Farming; n=1, 1Brazil; Student; n=1, 1Brazil; Paid employment; n=7, 7Brazil; Other; n=8, 7Colombia; Farming; n=2, 2Colombia; Paid employment; n=1, 1Peru; Housework; n=18, 18Peru, Farming; n=4, 4Peru; Student; n=3, 3Peru; Paid employment; n=1, 1Peru; Other; n=7, 7Thailand; Farming; n=1, 1Vietnam; Farming; n=4, 4Vietnam; Paid employment; n=0, 3
First Malaria Relapse Follow-up0000001154216112

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Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria

Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The number of participants or care givers who had taken off from their normal occupation due to relapse episode of P vivax malaria has been presented by country. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 180

InterventionParticipants (Number)
Brazil; Housework; n=2, 1Brazil; Farming; n=1, 1Brazil; Student; n=1, 1Brazil; Paid employment; n=7, 7Brazil; Other; n=8, 7Colombia; Housework; n=1, 0Colombia; Farming; n=2, 2Colombia; Paid employment; n=1, 1Peru; Housework; n=18, 18Peru, Farming; n=4, 4Peru; Student; n=3, 3Peru; Paid employment; n=1, 1Peru; Other; n=7, 7Thailand; Farming; n=1, 1Vietnam; Farming; n=4, 4
First Malaria Relapse0000010114421713

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Number of Participants With Abnormal Urinalysis Dipstick Results

Mid-stream urine was collected and analyzed for bilirubin, glucose, ketones, leukocyte esterase (LE), nitrites, occult blood, proteins and urobilinogen by dipstick method. The number of participants with abnormal urinalysis results (Trace, +, ++, +++, ++++) has been presented. Only those participants with data available at the specified data points were analyzed. (NCT02216123)
Timeframe: Up to Day 120

,
InterventionParticipants (Number)
Bilirubin, Day 1, TraceBilirubin, Day 1, +Bilirubin, Day1, ++Bilirubin, Day 3, +Bilirubin, Day 3, ++Bilirubin, Day 5, TraceBilirubin, Day 5, +Bilirubin, Day 8, +Bilirubin, Day 11, TraceBilirubin, Day 22, TraceBilirubin, Day 22, +Bilirubin, Day 60, TraceBilirubin, Day 60, +Bilirubin, Day 90, +Bilirubin, Day 120, +Glucose, Day 1, +Glucose, Day 1, ++Glucose, Day1, +++Glucose, Day1, ++++Glucose, Day 3, +Glucose, Day 3, ++Glucose, Day 3, +++Glucose, Day 3, ++++Glucose, Day 5, ++Glucose, Day 5, +++Glucose, Day 8, +Glucose, Day 8, ++Glucose, Day 8,+++Glucose, Day 11, TraceGlucose, Day 11, +Glucose, Day 11, ++Glucose, Day 11, +++Glucose, Day 15, ++Glucose, Day 15, +++Glucose, Day 15, ++++Glucose, Day 22, +Glucose, Day 22, +++Glucose, Day 29, TraceGlucose, Day 29, ++Glucose, Day 60, +Glucose, Day 60, ++Glucose, Day 90, +Glucose, Day 90, ++Glucose, Day 90, +++Glucose, Day 120, TraceGlucose, Day 120, +Glucose, Day 120, ++Glucose, Day 120, +++Glucose, Day 120, ++++Ketones, Day 1, TraceKetones, Day 1, +Ketones, Day1, ++Ketones, Day1, +++Ketones, Day 3, TraceKetones, Day 3, +Ketones, Day 3, ++Ketones, Day 3, +++Ketones, Day 5, +Ketones, Day 8, +Ketones, Day 11, TraceKetones, Day 22, TraceKetones, Day 22, +Ketones, Day 90, TraceKetones, Day 90, +Ketones, Day 90, ++Ketones, Day 120, TraceKetones, Day 120, +Ketones, Day 120, ++LE, Day 1, TraceLE, Day 1, +LE, Day1, ++LE, Day1, +++LE, Day 3, TraceLE, Day 3, +LE, Day 3, ++LE, Day 3, +++LE, Day 5, TraceLE, Day 5, +LE, Day 5, ++LE, Day 5, +++LE, Day 8, TraceLE, Day 8, +LE, Day 8, ++LE, Day 8, +++LE, Day 11, TraceLE, Day 11, +LE, Day 11, ++LE, Day 11, +++LE, Day 15, TraceLE, Day 15, +LE, Day 15, ++LE, Day 15, +++LE, Day 22, TraceLE, Day 22, +LE, Day 22, ++LE, Day 22, +++LE, Day 29, TraceLE, Day 29, +LE, Day 29, ++LE, Day 29, +++LE, Day 60, TraceLE, Day 60, +LE, Day 60, ++LE, Day 60, +++LE, Day 90, TraceLE, Day 90, +LE, Day 90, ++LE, Day 90, +++LE, Day 120, TraceLE, Day 120, +LE, Day 120, ++LE, Day 120, +++Nitrite, Day 1, TraceNitrite, Day 1, +Nitrite, Day 3, +Nitrite, Day 5, +Nitrite, Day 5, +++Nitrite, Day 8, +++Nitrite, Day 11, +Nitrite, Day 15, +Nitrite, Day 22, TraceNitrite, Day 29, +Nitrite, Day 60, +Nitrite, Day 90, TraceNitrite, Day 90, +Nitrite, Day 120, +Nitrite, Day 120, ++Occult blood, Day 1, TraceOccult blood, Day 1, +Occult blood, Day 1, ++Occult blood, Day1, +++Occult blood, Day1, ++++Occult blood, Day 3, TraceOccult blood, Day 3, +Occult blood, Day 3, ++Occult blood, Day 3, +++Occult blood, Day 3, ++++Occult blood, Day 5, TraceOccult blood, Day 5, +Occult blood, Day 5, ++Occult blood, Day 5, +++Occult blood, Day 5, ++++Occult blood, Day 8, TraceOccult blood, Day 8, +Occult blood, Day 8, ++Occult blood, Day 8,+++Occult blood, Day 11, TraceOccult blood, Day 11, +Occult blood, Day 11, ++Occult blood, Day 11, +++Occult blood, Day 11, ++++Occult blood, Day 15, TraceOccult blood, Day 15, +Occult blood, Day 15, ++Occult blood, Day 15, +++Occult blood, Day 15, ++++Occult blood, Day 22, TraceOccult blood, Day 22, +Occult blood, Day 22, ++Occult blood, Day 22, +++Occult blood, Day 22, ++++Occult blood, Day 29, TraceOccult blood, Day 29, +Occult blood, Day 29, ++Occult blood, Day 29, +++Occult blood, Day 29, ++++Occult blood, Day 60, TraceOccult blood, Day 60, +Occult blood, Day 60, ++Occult blood, Day 60, +++Occult blood, Day 60, ++++Occult blood, Day 90, TraceOccult blood, Day 90, +Occult blood, Day 90, ++Occult blood, Day 90, +++Occult blood, Day 90, ++++Occult blood, Day 120, TraceOccult blood, Day 120, +Occult blood, Day 120, ++Occult blood, Day 120, +++Occult blood, Day 120, ++++Protein, Day 1, TraceProtein, Day 1, +Protein, Day1, ++Protein, Day 3, TraceProtein, Day 3, +Protein, Day 3, ++Protein, Day 5, TraceProtein, Day 5, +Protein, Day 5, ++Protein, Day 8, TraceProtein, Day 8, +Protein, Day 8,++Protein, Day 11, TraceProtein, Day 11, +Protein, Day 11, ++Protein, Day 15, +Protein, Day 15, ++Protein, Day 22, TraceProtein, Day 22, +Protein, Day 22, ++Protein, Day 29, TraceProtein, Day 29, +Protein, Day 29, ++Protein, Day 60, TraceProtein, Day 60, +Protein, Day 60, ++Protein, Day 90, TraceProtein Day 90, +Protein, Day 120, TraceProtein, Day 120, +Protein, Day 120, ++Urobilinogen, Day 1, TraceUrobilinogen, Day 1, +Urobilinogen, Day1, ++Urobilinogen, Day1, +++Urobilinogen, Day 3, TraceUrobilinogen, Day 3, +Urobilinogen, Day 3, ++Urobilinogen Day 3, +++Urobilinogen, Day 3, ++++Urobilinogen, Day 5, TraceUrobilinogen, Day 5, +Urobilinogen, Day 8, TraceUrobilinogen, Day 8, +Urobilinogen, Day 8, ++Urobilinogen, Day 8,+++Urobilinogen, Day 11, TraceUrobilinogen, Day 11, +Urobilinogen, Day 11, ++Urobilinogen, Day 15, TraceUrobilinogen, Day 15, +Urobilinogen, Day 15, ++Urobilinogen, Day 22, TraceUrobilinogen, Day 29, TraceUrobilinogen, Day 29, +Urobilinogen, Day 60, TraceUrobilinogen, Day 60, +Urobilinogen, Day 90, TraceUrobilinogen, Day 90, +Urobilinogen, Day 120, TraceUrobilinogen, Day 120, +Urobilinogen, Day 120, ++
PQ+CQ12030002110111211311121131111201101210241111012200231132001010010000192205101422341223312831240106403421172113210000001000011104742136331133224402132011221115111251400730017232253028816131511420310001101001201010005412114311222111011000111010001
TQ+CQ1938214010102032020010000100003101010110100111001344205331111120111131951413213113371062611338442413315111488526132051250141111121230221218912641495347643412332833121132041142151733151523141374221336015194821354266114121221341331432618231036148003320001203113423143220

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Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria

Health outcomes were evaluated based on the actions taken by the participants to treat relapse episode of P vivax malaria. The number of participants with the type of action taken to treat relapse episode of P vivax malaria has been presented by country. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 180

,
InterventionParticipants (Number)
Brazil; Trial clinic; n=19, 17Brazil; Other; n=19, 17Colombia; Nothing; n=4, 3Colombia; Trial clinic; n=4, 3Colombia; Another clinic; n=4, 3Colombia; Hospital emergency center; n=4, 3Peru; Trial clinic; n=33, 33Peru; Another clinic; n=33, 33Peru; Other; n=33, 33Thailand; Nothing; n=1, 1Thailand; Trial Clinic; n=1, 1Vietnam; Nothing; n=4, 7Vietnam; Drug Shop; n=4, 7Vietnam; Other; n=4, 7Vietnam; Another clinic; n=4, 7
First Malaria Relapse19521113289101210
First Malaria Relapse Follow-up170200133330015201

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Number of Participants With Change in Best Corrected Visual Acuity Test Scores

Ophthalmic assessments were carried out at pre-qualified sites prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline is the value at post dose visit minus the Baseline value. Best corrected visual acuity was assessed individually for each eye. Scores were recorded as a ratio. The values were used to derive a logMAR score for statistical analysis where logMAR=-1x log10 (ratio score). The number of participants with change in Best Corrected Visual Acuity Test Scores from Baseline has been presented where possible change is defined as a change from Baseline >=0.12 to <0.3 and definite change is defined as a change from Baseline >=0.3 logMAR score. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Baseline and up to Day 180

,
InterventionParticipants (Number)
Maximum change; possible; right eye; n=27, 13Maximum change; definite; right eye; n=27, 13Maximum change; possible; left eye; n=27, 13Maximum change; definite; left eye; n=27, 13Day 29; possible change; right eye; n=27, 13Day 29; definite change; right eye; n=27, 13Day 29; possible change; left eye; n=27, 13Day 29; definite change; left eye; n=27, 13Day 90; possible change; right eye; n=27, 12Day 90; definite change; right eye; n=27, 12Day 90; possible change; left eye; n=27, 12Day 90; definite change; left eye; n=27, 12Day 180; possible change; right eye; n=2, 2Day 180; definite change; right eye; n=2, 2Day 180; possible change; left eye; n=2, 2Day 180; definite change; left eye; n=2, 2
PQ+CQ0001000000000001
TQ+CQ1021102000210000

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Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range

Plasma or serum samples were anlalyzed to evaluate clinical chemistry parameters such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, creatine kinase, creatinine, glomerular filtration rate (GFR), indirect bilirubin and urea. The number of participants with clinical chemistry laboratory values outside the extended normal range (F3) has been presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Safety Population consisted of all randomized participants who received at least one dose of blinded study medication. (NCT02216123)
Timeframe: Up to Day 120

,
InterventionParticipants (Number)
ALT, HighALP, HighAST, HighBilirubin, HighCreatine kinase, HighCreatinine, HighGFR, LowIndirect bilirubin, HighUrea, High
PQ+CQ013184002119
TQ+CQ806283003640

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Number of Participants With Electrocardiogram (ECG) Findings

12 lead ECG was performed with the participant in a semi-supine position having rested in this position for at least 10 minutes. ECG assessments were performed in triplicate at screening followed by single ECGs 12 hours after the first dose of study medication and at Day 29. The number of participants with abnormal-clinically significant ECG findings have been presented. The 12 Hour Post Randomized Treatment (11.5-12.5 Hours) timepoint included all readings taken between 11.5 and 12.5 hours post randomized treatment. The 12 Hour Post Randomized Treatment (8-72 Hours) timepoint is a sensitivity analysis of the 12 Hour post randomized treatment timepoint, including all readings taken between 8 and 72 hours post randomized treatment. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 29

,
InterventionParticipants (Number)
11.5 to 12.5 hours Day 1, Assessment 1; n=143, 7511.5 to 12.5 hours Day 1 Assessment 2; n=6, 611.5 to 12.5 hours Day 1 Assessment 3; n=5, 58 to 72 hours Day 1 Assessment 1; n=166, 858 to 72 hours Day 1 Assessment 2; n=6, 68 to 72 hours Day 1 Assessment 3; n=5, 5Day 29; n=161, 84
PQ+CQ0000000
TQ+CQ0000000

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Number of Participants With Genetically Homologous and Genetically Heterologous P. Vivax Infections

Two drops of peripheral blood were collected onto pre-printed filter paper for subsequent deoxyribonucleic acid (DNA) extraction and polymerase chain reaction (PCR) analysis of Plasmodium species on all participants at screening (Day 1; pre-dose) and; if necessary, at the time of the first recrudescence/relapse or re-infection. PCR of the P. vivax genes, was used to distinguish between genetically homologous and genetically heterologous infection. The number of participants with genetically homologous and genetically heterologous P. vivax infections has been summarized for each treatment group. Only those participants with an infection occuring on or after Study Day 33 were analyzed. (NCT02216123)
Timeframe: Up to Day 180

,
InterventionParticipants (Number)
Heterologous P. vivaxHomologous P. vivaxUnknown genetic classification
PQ+CQ9101
TQ+CQ8295

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Number of Participants With Hematology Laboratory Data Outside the Reference Range

Blood samples were collected for the evaluation of hematology parameters including eosinophils, leukocytes, lymphocytes, neutrophils, platelets, reticulocytes and methemoglobin. The number of participants with hematology laboratory data outside the extended normal range (F3) has been presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Participants having both High and Low values for Normal Ranges at any post-baseline visits for safety parameters were counted in both the High and Low categories. (NCT02216123)
Timeframe: Up to Day 120

,
InterventionParticipants (Number)
Blood eosinophils, HighBlood leukocytes, LowBlood lymphocytes, LowBlood lymphocytes, HighBlood neutrophils, LowBlood platelets, LowBlood reticulocytes, HighMethemoglobin, High
PQ+CQ1501438393
TQ+CQ320811513802

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Number of Participants With Keratopathy

Ophthalmic assessments were carried out at pre-qualified sites prior to randomization and at Days 29 and 90 and at withdrawal follow-up visit. Assessments were carried out at Day 180 (and up to resolution) if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. The number of participants displaying keratopathy in each eye has been summarized for each visit. The number of participants with new keratopathy at any time post Baseline is also reported. Ophthalmic Safety Population comprised of all participants in the Safety Population who have results from any eye assessments. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Up to Day 180

,
InterventionParticipants (Number)
Baseline; right eye; n=27, 13Baseline; left eye; n=27, 13Day 1; right eye; n=27, 13Day 1; left eye; n=27, 13Day 29; right eye; n=27, 13Day 29; left eye; n=27, 13Day 90; right eye; n=27, 12Day 90; left eye; n=27, 12Day 180; right eye; n=2, 2Day 180; left eye; n=2, 2Any time post Baseline; right eye; n=27, 13Any time post Baseline; left eye; n=27, 13
PQ+CQ000000000000
TQ+CQ000000000000

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Number of Participants With Retinal Changes From Baseline

Ophthalmic assessments were carried out at pre-qualified sites prior to randomization and at Days 29 and 90 and at withdrawal follow-up. Assessments were carried out at Day 180 (and up to resolution) if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline was calculated as the value at post dose visit minus the Baseline value. The number of participants with definite retinal change and questionable (ques) retinal change from Baseline has been presented. The number of participants with maximum change post-Baseline (definite when absent or questionable at Baseline) has been presented for either eye. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). (NCT02216123)
Timeframe: Baseline and up to Day 180

,
InterventionParticipants (Number)
Day 29, Definite change, right eye; n=22, 13Day 29, Ques change, right eye; n=22, 13Day 29, Definite change, left eye; n=22, 13Day 29, Ques change, left eye; n=22, 13Day 90, Definite change, right eye; n=24, 11Day 90, Ques change, right eye; n=24, 11Day 90, Definite change, left eye; n=24, 11Day 90, Ques change, left eye; n=24, 11Day 180, Definite change, right eye; n=3, 2Day 180, Ques change, right eye; n=3, 2Day 180, Definite change, left eye; n=3, 2Day 180, Ques change, left eye; n=3, 2Maximum change post-Baseline; either eye; n=27, 13
PQ+CQ0000010000000
TQ+CQ0201020000000

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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) is defined as any untoward medical occurrence in a participant under clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations such as important medical events and events of possible drug induced liver injury with hyperbilirubinemia. TEAEs are defined as AEs with an onset date and time on or after that of the start of first dose of study medication (including CQ). Number of participants with TEAEs and serious TEAEs have been presented. (NCT02216123)
Timeframe: Up to Day 180

,
InterventionParticipants (Number)
TEAEsSerious TEAEs
PQ+CQ641
TQ+CQ1196

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Time to a Single Positive Smear

Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. 95.5% confidence intervals were constructed for the relative risk. (NCT02488980)
Timeframe: 24 Weeks

,,
InterventionDays (Median)
First positive smearTwo consecutive positve smears
Mefloquine50165
Placebo4363
Tafenoquine570

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Safety (SAEs and AEs)

The most commonly reported experiences in subject occurring in at least 20% of subjects in any treatment group. (NCT02488980)
Timeframe: 28 weeks

,,
Interventionparticipants (Number)
At least one AEHeadacheUpper Respiratory Tract InfectionBack PainMyalgiaAbdominal PainCoughingRhinitis
Mefloquine9749261029192920
Placebo9237171225241321
Tafenoquine9845302827252412

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Prophylactic Outcome Defined by the Subject Having no Positive Smears

Prophylactic outcome (success/failure) at the end of the prophylactic treatment phase; outcome was based on absence/presence of asexual stage parasites of any Plasmodium species on a single blood smear. (NCT02488980)
Timeframe: 24 Weeks

,,
Interventionparticipants (Number)
Prophylactic FailureProphylactic Success (total)Prophylactic Success (known)Prophylactic Success (assumed)
Mefloquine92707
Placebo93606
Tafenoquine901266

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Protective Efficacy Based on Two Consecutive Positive Smears

Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. Analysis was based on a calculation of protective efficacy (PE) of tefaenoquine, defined as (1-relative risk of developing parasitaemia tafenoquine: placebo) x100% and 95.5% confidence intervals were constructed for the relative risk using Koopman's method. (NCT02488980)
Timeframe: 24 Weeks

InterventionPercentage of Protective Efficacy (Number)
Placebo0
Tafenoquine77.9
Mefloquine56.8

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Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

"Blood samples were collected for analysis of eosinophils, lymphocytes, platelets and reticulocytes. PCI ranges were >1.5*10^9 (high) cells per liter (cells/L) for eosinophils, <0.5*10^9 cells/L (low) or >4*10^9 cells/L (high) for lymphocytes, <50*10^9 cells/L (low) for platelet count and >1*upper limit of normal (ULN) 10^12 cells/L (high) for reticulocyte count. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline value is the latest pre-tafenoquine dose assessment on Day 1." (NCT02563496)
Timeframe: Baseline (Day 1) and up to Day 8

,,,
InterventionParticipants (Count of Participants)
Eosinophils: To LowEosinophils: To within Range or No ChangeEosinophils: To HighLymphocytes: To LowLymphocytes: To within Range or No ChangeLymphocytes: To HighPlatelet count: To LowPlatelet count: To within Range or No ChangePlatelet count: To HighReticulocyte count: To LowReticulocyte count: To within Range or No ChangeReticulocyte count: To High
Tafenoquine 100 mg012209501400131
Tafenoquine 150 mg041032050050
Tafenoquine 200 mg0202020202200184
Tafenoquine 300 mg0181016301900154

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Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

"Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were >3*ULN international units per liter (IU/L) (alanine aminotransferase [ALT]), >2.5*ULN IU/L (alkaline phosphatase), >3*ULN IU/L (aspartate aminotransferase [AST]), >1.5*ULN micromoles/L (mcmol/L) (bilirubin), >5*ULN IU/L (creatine kinase [CK]), 3*ULN mcmol/L (creatinine), >1.5*ULN mcmol/L (indirect bilirubin), and >11.067 millimoles/L (urea). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the To within Range or No Change category. Participants were counted twice if participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline value is the latest pre-Tafenoquine dose assessment on Day 1." (NCT02563496)
Timeframe: Baseline (Day 1) and up to Day 8

,,,
InterventionParticipants (Count of Participants)
ALT: To LowALT: To within Range or No ChangeALT: To HighAlkaline phosphatase: To LowAlkaline phosphatase: To within Range or No ChangeAlkaline phosphatase: To HighAST: To LowAST: To within Range or No ChangeAST: To HighBilirubin: To LowBilirubin: To within Range or No ChangeBilirubin: To HighCK: To LowCK: To within Range or No ChangeCK: To HighCreatinine: To LowCreatinine: To within Range or No ChangeCreatinine: To HighIndirect bilirubin: To LowIndirect bilirubin: To within Range or No ChangeIndirect bilirubin: To HighUrea: To LowUrea: To within Range or No ChangeUrea: To High
Tafenoquine 100 mg01400140014001400140014001400140
Tafenoquine 150 mg050050050050050050050050
Tafenoquine 200 mg02200211022002200220022002200220
Tafenoquine 300 mg01900190019001900190019001900190

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Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury. (NCT02563496)
Timeframe: Up to Day 120

,,,
InterventionParticipants (Count of Participants)
Non-SAEsSAEs
Tafenoquine 100 mg100
Tafenoquine 150 mg40
Tafenoquine 200 mg100
Tafenoquine 300 mg131

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Number of Participants With Hemoglobin Decline From Baseline Over First 10 Days

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is known to be a risk factor for hemolysis in participants treated with 8-aminoquinolines. Blood samples were collected for the evaluation of hemoglobin levels. Hemoglobin decrease of >=30 percent (%) of >30 grams per liter (g/L) from Baseline; or, an overall drop in hemoglobin below 60.0 g/L in the first 15 days of the study were considered as protocol defined serious adverse events (SAEs). Number of participants with hemoglobin decline from Baseline over first 10 days have been presented. Baseline was defined as the latest pre-tafenoquine dose assessment on Day 1. (NCT02563496)
Timeframe: Baseline and up to Day 10

,,,
InterventionParticipants (Count of Participants)
<=20 g/L>20 g/L to <=30 g/L>30 g/L or >=30%
Tafenoquine 100 mg1400
Tafenoquine 150 mg500
Tafenoquine 200 mg2110
Tafenoquine 300 mg1900

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Number of Participants With Gastrointestinal Adverse Events

Number of participants experiencing gastrointestinal adverse events including vomiting, abdominal pain, diarrhea, gastrointestinal disorder, epigastric discomfort and nausea were assessed. Number of participants with gastrointestinal adverse events for each treatment group have been presented. Safety Population consisted of all participants who received at least one dose of study medication (tafenoquine). (NCT02563496)
Timeframe: Up to Day 120

,,,
InterventionParticipants (Count of Participants)
VomitingAbdominal painDiarrheaGastrointestinal disorderEpigastric discomfortNausea
Tafenoquine 100 mg202000
Tafenoquine 150 mg300100
Tafenoquine 200 mg131100
Tafenoquine 300 mg600011

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Number of Participants With Relapse-Free Efficacy at 4 Months

Relapse is defined as positive blood smear with or without vivax malaria symptoms. A participant was considered to have demonstrated relapse-free efficacy if: a) Participant is slide positive for Plasmodium vivax (P. vivax) at Baseline. b) Participant showed initial clearance of P. vivax parasitemia defined as a negative slide at or before the Day 29 visit. c) Participant is not slide-positive for P. vivax at any assessment. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 4 months defined as a negative asexual P. vivax parasite slide at the first parasite assessment performed during study. Microbiologic-Intent-To-Treat (mITT) Population consisted of all participants who received a dose of study treatment (tafenoquine) and had microscopically-confirmed vivax parasitemia at Baseline. (NCT02563496)
Timeframe: 4 months

InterventionParticipants (Count of Participants)
Tafenoquine 100 mg12
Tafenoquine 150 mg4
Tafenoquine 200 mg20
Tafenoquine 300 mg17

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Area Under the Curve From Time 0 Extrapolated to Infinite Time (AUC[0-infinity]) of Tafenoquine by Weight Band in Participants Aged >=2 Years to <16 Years (Weighing >=5 kg)

Blood samples were collected at indicated time points for pharmacokinetic analysis of tafenoquine. Pharmacokinetic parameters were determined using standard non-compartmental methods. AUC(0-infinity) of tafenoquine was evaluated for participants aged >=2 years to <16 years (weighing >=5 kg). Pharmacokinetic (PK) population consisted of all participants with at least one PK sample taken at Days 3, 15, 29 and 60, with accurate dosing and sample time histories. (NCT02563496)
Timeframe: Days 3, 15, 29 and 60 post dose

InterventionHours*microgram per milliliter (Median)
Tafenoquine 100 mg85.1
Tafenoquine 150 mg154.7
Tafenoquine 200 mg111.4
Tafenoquine 300 mg120.8

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Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Results Relative to Normal Range Post-Baseline Relative to Baseline

"SBP and DBP were measured with participants in semi-supine position after 5 minutes of rest. Data was categorized as: systolic blood pressure (SBP) (low: <90 and high: >120 millimeters of mercury [mmHg]); diastolic blood pressure (DBP) (low: <60 and high: >80 mmHg); and 'To Normal or No change'. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose vital sign value category was unchanged (e.g.,High to High), or whose value became normal, are recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Day 1 was considered as Baseline." (NCT02802501)
Timeframe: Baseline (Day 1) and up to Day 180

,,
InterventionParticipants (Count of Participants)
SBP, To LowSBP, To Normal or No changeSBP, To HighDBP, To LowDBP, To Normal or No changeDBP, To High
DHA-PQP Only01931111628
Primaquine+DHA-PQP02525151628
Tafenoquine+ DHA-PQP1212992025

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Number of Participants With Worst Case Respiratory Rate Results Relative to Normal Range Post-Baseline Relative to Baseline

"Respiratory rate was measured with participants in semi-supine position after 5 minutes of rest. Data was categorized as: respiratory rate low: <12 breaths per minute', high: >18 breaths per minute and 'To normal or No change'. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose vital sign value category was unchanged (e.g.,High to High), or whose value became normal, are recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.Day 1 was considered as Baseline. Day 1 was considered as Baseline." (NCT02802501)
Timeframe: Baseline (Day 1) and up to Day 180

,,
InterventionParticipants (Count of Participants)
To LowTo Normal or No changeTo High
DHA-PQP Only0419
Primaquine+DHA-PQP04010
Tafenoquine+ DHA-PQP0419

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Number of Participants With Worst Case Pulse Rate Results Relative to Normal Range Post-Baseline Relative to Baseline

"Pulse rate was measured with participants in semi-supine position after 5 minutes of rest. Data was categorized as: pulse rate low: <60 beats per minute [bpm], high: >100 bpm and 'To normal or No change'. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose vital sign value category was unchanged (e.g.,High to High), or whose value became normal, are recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Day 1 was considered as Baseline." (NCT02802501)
Timeframe: Baseline (Day 1) and up to Day 180

,,
InterventionParticipants (Count of Participants)
To LowTo Normal or No changeTo High
DHA-PQP Only19257
Primaquine+DHA-PQP23263
Tafenoquine+ DHA-PQP26236

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Number of Participants With Worst Case Body Temperature Results Relative to Normal Range Post-Baseline Relative to Baseline

"Body temperature was measured with participants in semi-supine position after 5 minutes of rest. Data was categorized as: body temperature 'low: <36.5 degrees celsius', 'high: >37.3 degrees celsius' and 'To Normal or No change'. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose vital sign value category was unchanged (e.g.,High to High), or whose value became normal, are recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Day 1 was considered as Baseline." (NCT02802501)
Timeframe: Baseline (Day 1) and up to Day 180

,,
InterventionParticipants (Count of Participants)
To LowTo Normal or No changeTo High
DHA-PQP Only42310
Primaquine+DHA-PQP4256
Tafenoquine+ DHA-PQP38714

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Number of Participants With Protocol-defined SAE (Hemoglobin Drop)

Blood samples were collected at indicated time points to analyze the hemoglobin level. Hemoglobin drop is defined as any one of the following occurring in the first 15 days of the study: a relative hemoglobin decrease of >=30% from Baseline, or an absolute hemoglobin decrease of >3 grams per liter from Baseline, or a drop in absolute hemoglobin to <7.0 grams per decilter (g/dL). Number of participants with a protocol-defined hemoglobin SAEs has been presented. (NCT02802501)
Timeframe: Days 3, 5, 7, and 14

,,
InterventionParticipants (Count of Participants)
Day 3Day 5Day 7Day 14
DHA-PQP Only0000
Primaquine+DHA-PQP0000
Tafenoquine+ DHA-PQP0000

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Number of Participants With Hematology Values Outside Clinical Concern Range

Blood samples were collected to analyze the following hematology parameters: Hemoglobin, lymphocytes and Platelet count. The clinical concern ranges for the parameters included: hemoglobin (low: <7 grams per deciliter), lymphocytes: (low: <0.5x10^9 cells per liter and high: >4x10^9 cells per liter),and platelets (low: <50x10^9 cells per liter). Data for any time on treatment has been presented. (NCT02802501)
Timeframe: Up to Day 120

,,
InterventionParticipants (Count of Participants)
Hemoglobin, LowLymphocytes, HighLymphocytes, LowPlatelets, Low
DHA-PQP Only0300
Primaquine+DHA-PQP0210
Tafenoquine+ DHA-PQP0401

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Number of Participants With Gastrointestinal AEs

The number of participants with gastrointestinal AEs: nausea, vomiting, diarrhea, dyspepsia, abdominal distension, abdominal discomfort and constipation has been presented. (NCT02802501)
Timeframe: Up to Day 180

,,
InterventionParticipants (Count of Participants)
NauseaVomitingDiarrheaDyspepsiaAbdominal distensionAbdominal discomfortConstipation
DHA-PQP Only5652100
Primaquine+DHA-PQP3124120
Tafenoquine+ DHA-PQP4523101

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Time to Parasite Clearance

Parasite clearance time is defined as time needed to clear asexual parasite from the blood that is, parasite numbers falling below the limit of detection in the thick blood smear and remaining undetectable after >= 6 hours later. The time to achieve parasite clearance was analyzed by Kaplan-Meier method. (NCT02802501)
Timeframe: Up to Day 8

InterventionHours (Median)
DHA-PQP Only18.1
Tafenoquine+ DHA-PQP18.1
Primaquine+DHA-PQP18.0

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Number of Participants With Chemistry Values Outside Clinical Concern Range

Blood samples were collected at indicated time points to analyze following chemistry parameters: alanine aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin, Creatine Kinase, Creatinine, Indirect Bilirubin and Urea. Clinical concern range for the parameters included ALT and AST (high: >3 times Upper Limit of Normal [ULN]), ALP (high: >2.5 times ULN), bilirubin and indirect bilirubin (high: >1.5 times ULN), creatine kinase (high: >5 times ULN), creatinine (high: >3 times ULN) and urea (high: >11.067 millimoles per Liter [mmol/L]. Data for any time on treatment has been presented. (NCT02802501)
Timeframe: Up to Day 120

,,
InterventionParticipants (Count of Participants)
ALT, HighALP, HighAST, HighBilirubin, HighCreatine Kinase, HighCreatinine, HighIndirect bilirubin, HighUrea, High
DHA-PQP Only11047010
Primaquine+DHA-PQP00046010
Tafenoquine+ DHA-PQP30166010

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Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Double-blind Treatment Phase

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function, other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. (NCT02802501)
Timeframe: Up to Day 180

,,
InterventionParticipants (Count of Participants)
Any AEsAny SAEs
DHA-PQP Only411
Primaquine+DHA-PQP342
Tafenoquine+ DHA-PQP412

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Change From Baseline in QT Interval Corrected by Fridericia's Formula (QTcF)

12-lead ECG was obtained at indicated time points using an automated ECG machine that measured QTcF interval. Change from Baseline is calculated as Post-Dose Visit Value minus Baseline value. Day 1 was considered as Baseline. (NCT02802501)
Timeframe: Baseline (Day 1), Day 3: 4 hours post DHA-PQP dose, Days 7 and 28

,,
InterventionMilliseconds (Mean)
Day 3: 4 hours post DHA-PQP doseDay 7Day 28
DHA-PQP Only35.311.52.4
Primaquine+DHA-PQP40.816.510.2
Tafenoquine+ DHA-PQP44.512.27.5

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Change From Baseline in Methemoglobin/ Total Hemoglobin

Blood samples were collected for the assessment of methemoglobin/Total Hemoglobin (Hb). Methemoglobin is a type of Hb in the form of metalloprotein that cannot bind with oxygen, measured as percentage of methemoglobin in total hemoglobin. Change from Baseline is calculated as Post-Dose Visit Value minus Baseline value. Day 1 was considered as Baseline. (NCT02802501)
Timeframe: Baseline (Day 1) and Days 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,18,20,21,22,24,26,28 and 60

,,
InterventionPercentage of Methemoglobin in total Hb (Mean)
Day 2, n=48, 50, 50Day 3, n=48, 50, 50Day 4, n=48, 50, 50Day 5, n=48, 50, 50Day 6, n=46, 49, 50Day 7, n=48, 50, 50Day 8, n=46, 48, 48Day 9, n=46, 47, 47Day 10, n=47, 45, 49Day 11, n=47, 44, 49Day 12, n=47, 47, 50Day 13, n=48, 48, 48Day 14, n=48, 50, 50Day 15, n=17, 22, 14Day 16, n=43, 48, 47Day 18, n=46, 48, 49Day 20, n=42, 49, 48Day 21, n=43, 48, 48Day 22, n=45, 49, 48Day 24, n=41, 46, 47Day 26, n=44, 45, 47Day 28, n=47, 50, 50Day 60, n=47, 50, 49
DHA-PQP Only-0.13-0.16-0.16-0.18-0.15-0.19-0.12-0.13-0.16-0.13-0.13-0.14-0.18-0.08-0.12-0.12-0.09-0.07-0.13-0.11-0.17-0.15-0.11
Primaquine+DHA-PQP-0.060.010.280.620.911.201.411.531.691.821.922.022.012.131.841.290.800.690.490.410.190.08-0.01
Tafenoquine+ DHA-PQP-0.07-0.040.060.120.160.190.230.240.240.180.180.180.120.000.120.110.060.030.010.030.030.01-0.07

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Time to Relapse of P. Vivax Malaria

Relapse is defined by a positive blood smear with or without vivax symptoms. Relapse is described as any recurrence of P. vivax malaria after clearance of the initial infection. The time to relapse (number of days between the date of first positive count and date of Study Day 1) was analyzed by the Kaplan-Meier method. The median number of days to relapse along with 95 percent (%) confidence interval (CI) has been presented for each treatment group. (NCT02802501)
Timeframe: Up to Day 180

InterventionDays (Median)
DHA-PQP Only81.5
Tafenoquine+ DHA-PQP96.0
Primaquine+DHA-PQPNA

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Time to Fever Clearance

Time to fever clearance is defined as time from first dose of treatment to the time when body temperature falls to normal and remains normal for at least 48 hours up to the Day 7 visit. Fever clearance is considered to have been achieved once an initial temperature of greater than 37.4 degree Celsius is reduced to a value less than or equal to 37.4 degree Celsius, in the absence of value greater than 37.4 degree Celsius in the following 48 hours up to Day 7 visit. The time taken to achieve fever clearance was analyzed by Kaplan-Meier method. (NCT02802501)
Timeframe: Up to Day 7

InterventionHours (Median)
DHA-PQP Only16.5
Tafenoquine+ DHA-PQP15.8
Primaquine+DHA-PQP16.8

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Percentage of Participants With Relapse-free Efficacy at Six Months After Administration of Tafenoquine With DHA-PQP and Primaquine+DHA-PQP

A participant was considered to have demonstrated relapse-free efficacy at 6 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline (Day 1), b) Participant demonstrated initial clearance of P.vivax parasitemia, c) Participant had no positive asexual P.vivax parasite count at any assessment prior to or on study Day 180 following initial parasite clearance, d) Participants did not take a concomitant medication with anti-malarial activity (excluding study treatment) at any point between Study Day 1 and their last parasite assessment, e) Participant was parasite-free at 6 months. The percentage of participants who were relapse-free at 6 months post dose has been presented. (NCT02802501)
Timeframe: 6 months post-dose

InterventionPercentage of participants (Number)
Tafenoquine+ DHA-PQP22
Primaquine+DHA-PQP52

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Percentage of Participants With Relapse-free Efficacy at Six Months After Administration of Tafenoquine With DHA-PQP and DHA-PQP Alone

A participant was considered to have demonstrated relapse-free efficacy at 6 months if: a) Participant had non-zero Plasmodium vivax (P.vivax) asexual parasite count at Baseline (Day 1), b) Participant demonstrated initial clearance of P.vivax parasitemia, c) Participant had no positive asexual P.vivax parasite count at any assessment prior to or on study Day 180 following initial parasite clearance, d) Participants did not take a concomitant medication with anti-malarial activity (excluding study treatment) at any point between Study Day 1 and their last parasite assessment, e) Participant was parasite-free at 6 months. The percentage of participants who were relapse-free at 6 months post dose has been presented. (NCT02802501)
Timeframe: 6 months post-dose

InterventionPercentage of participants (Number)
DHA-PQP Only12
Tafenoquine+ DHA-PQP22

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Percentage of Participants With Relapse-free Efficacy at Six Months After Administration of Primaquine With DHA-PQP and DHA-PQP Alone

A participant was considered to have demonstrated relapse-free efficacy at 6 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline (Day 1), b) Participant demonstrated initial clearance of P.vivax parasitemia, c) Participant had no positive asexual P.vivax parasite count at any assessment prior to or on study Day 180 following initial parasite clearance, d) Participants did not take a concomitant medication with anti-malarial activity (excluding study treatment) at any point between Study Day 1 and their last parasite assessment, e) Participant was parasite-free at 6 months. The percentage of participants who were relapse-free at 6 months post dose has been presented. (NCT02802501)
Timeframe: 6 months post-dose

InterventionPercentage of participants (Number)
DHA-PQP Only12
Primaquine+DHA-PQP52

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Percentage of Participants With Relapse-free Efficacy at Four Months After Administration of Tafenoquine With DHA-PQP and DHA-PQP Alone

A participant was considered to have demonstrated recurrence-free efficacy at 4 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline, b) Participant demonstrated initial clearance of P.vivax parasitemia, c) Participant had no positive asexual P.vivax parasite count at any assessment prior to or on Study Day 135 following initial parasite clearance, d) Participants did not take a concomitant medication with anti-malarial activity (excluding study treatment) at any point between Study Day 1 and their first parasite assessment after Study Day 105 (up to and including Study Day 135), e) Participant was parasite-free at 4 months. The rate of relapse-free efficacy was estimated by Kaplan-Meier methodology. The percentage of participants who were relapse-free at 4 months post dose has been presented. (NCT02802501)
Timeframe: 4 months post-dose

InterventionPercentage of participants (Number)
DHA-PQP Only16
Tafenoquine+ DHA-PQP28

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Number of Participants With Recrudescence

Recrudescence was defined as blood stage treatment failure. A participant was considered to have had a recrudescence if both of the following were true: 1) if participant had a positive P. vivax asexual parasite count at Baseline and demonstrated clearance (i.e. two negative asexual P. vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval); 2) Participant had a positive genetically homologous asexual P. vivax parasite count on or before Study Day 14, after their zero count in days 1 to 5. (NCT02802501)
Timeframe: Up to Day 14

InterventionParticipants (Count of Participants)
DHA-PQP Only0
Tafenoquine+ DHA-PQP0
Primaquine+DHA-PQP0

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Number of Participants With Electrocardiogram (ECG) Values Outside Clinical Concern Range-QT Interval Corrected Using Fredericia's Formula (QTcF)

12-lead ECG was obtained at indicated time points using an automated ECG machine that measured QTcF. Clinical concern range included:absolute QTcF interval (upper: >480 milliseconds) and increase from Baseline in QTcF (upper: >=60 milliseconds). Data for maximum post-Baseline increase >=60 and >480 milliseconds has been presented. (NCT02802501)
Timeframe: Up to Day 28

InterventionParticipants (Count of Participants)
DHA-PQP Only2
Tafenoquine+ DHA-PQP3
Primaquine+DHA-PQP1

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